{"id":2253,"date":"2022-01-20T20:25:45","date_gmt":"2022-01-20T12:25:45","guid":{"rendered":"http:\/\/www.qhsxzh.com\/?p=2253"},"modified":"2024-12-29T15:03:29","modified_gmt":"2024-12-29T07:03:29","slug":"%e5%80%aa%e6%b5%b7%e5%8e%a6%e6%ad%a3%e5%bc%8f%e8%ae%ba%e6%96%87%e5%8c%ba%ef%bc%9a%e6%89%8b%e6%9c%af%e5%8c%96%e7%96%97%e4%b8%8e%e6%94%be%e5%b0%84%e7%ba%bf%e7%96%97%e4%bc%9a%e5%af%b9%e8%82%bf%e7%98%a4","status":"publish","type":"post","link":"https:\/\/www.qhsxzh.com\/?p=2253","title":{"rendered":"\u502a\u6d77\u53a6||\u6b63\u5f0f\u8bba\u6587\u533a\uff1a\u624b\u672f\u5316\u7597\u4e0e\u653e\u5c04\u7ebf\u7597\u4f1a\u5bf9\u80bf\u7624\u52a0\u901f\u6269\u6563\u7684\u7814\u7a76"},"content":{"rendered":"
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\n\t\u4ee5\u4e2d\u548c\u6297\u4f53\u6291\u5236\u80bf\u7624\u6210\u957f\u56e0\u5b50<\/strong>β <\/strong>\u53ef\u907f\u514d\u56e0\u653e\u5c04\u6cbb\u7597\u5f15\u8d77\u7684\u80bf\u7624\u52a0\u901f\u8f6c\u79fbnhx490<\/strong><\/h4>\n<\/section>\n
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\n\t(Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression)<\/strong><\/em><\/h4>\n

\"\" \u671f\u520a\uff1a<\/strong> \u4e34\u5e8a\u7814\u7a76\u671f\u520a (The Journal of Clinical Investigation)  Volume 117  Number 5  May 2007 \u4f5c\u8005<\/strong> Swati Biswas,1<\/sup> Marta Guix,2<\/sup> Cammie Rinehart,2<\/sup> Teresa C. Dugger,2<\/sup> Anna Chytil,1<\/sup> Harold L. Moses,1,3,4<\/sup> Michael L. Freeman,5<\/sup> and Carlos L. Arteaga1,2,4<\/sup> \u5355\u4f4d<\/strong> \u5c5e\u4e8e\u7f8e\u56fd\u7530\u7eb3\u897f\u5dde \u90a3\u4ec0\u7ef4\u5c14 \u8303\u5fb7\u5821\u5927\u5b66(Vanderbilt University) 1.\u764c\u75c7\u751f\u7269\u5b66\u7cfb\u30012.\u533b\u5b66\u7cfb\u30013.\u75c5\u7406\u5b66\u7cfb\u30014. Vanderbilt-Ingram\u764c\u75c7\u4e2d\u5fc3\u4e73\u764c\u7814\u7a76\u8ba1\u5212 \u4ee5\u53ca 5.\u653e\u5c04\u80bf\u7624\u5b66\u7cfb <\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u6458\u8981<\/strong><\/section>\n<\/section>\n
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\u6211\u4eec\u63a2\u7a76\u4e86\u56e0\u764c\u75c7\u6cbb\u7597\u800c\u4ea7\u751f\u7684TGF-β\u7a76\u7adf\u4f1a\u4e0d\u4f1a\u52a0\u901f\u80bf\u7624\u7684\u53d1\u751f\u3002\u6211\u4eec\u4f7f\u7528\u4e86MMTV\/PyVmT<\/em> \u6b64\u4e00\u8f6c\u79fb\u578b\u4e73\u764c\u57fa\u56e0\u7684\u8f6c\u6b96\u6a21\u578b\uff0c\u6307\u51fa\u4e86\u6e38\u79bb\u8f90\u5c04\uff08\u8bd1\u6ce81\uff09\u6216doxorubicin\uff08\u8bd1\u6ce82\uff09\u90fd\u4f1a\u589e\u52a0\u5faa\u73af\u4e2dTGF-β1\u4e0e\u80bf\u7624\u7ec6\u80de\u7684\u91cf\uff0c\u5e76\u4f1a\u589e\u52a0\u80ba\u90e8\u7684\u764c\u75c7\u8f6c\u79fb\u3002\u8fd9\u4e9b\u6548\u5e94\u90fd\u56e0\u4e3a\u6211\u4eec\u4f7f\u7528\u4e86\u6cdbTGF-β\u6297\u4f53\u800c\u53d7\u62b5\u9500\u3002\u6211\u4eec\u5728\u6709TGF-β\u6297\u4f53\u7684\u73af\u5883\u4e0b\uff0c\u4f53\u5916\u57f9\u517b\u4e86\u8fd9\u4e9b\u5728\u5faa\u73af\u4e2d\u4f1a\u8868\u73b0\u591a\u7624\u75c5\u6bd2\u4e2d\u7b49T\u6297\u539f\uff08\u8bd1\u6ce83\uff09\u7684\u80bf\u7624\u7ec6\u80de\uff0c\u53d1\u73b0\u5b83\u4eec\u4e0d\u4f1a\u751f\u957f\uff1b\u8fd9\u8868\u793aTGF-β\u5728\u8fd9\u4e9b\u7ec6\u80de\u4e2d\u662f\u4e00\u79cd\u751f\u5b58\u7684\u8baf\u53f7\u3002\u5f53\u8001\u9f20\u7684\u80bf\u7624\u4e0d\u542b\u6709\u7b2c\u4e8c\u578bTGF-β\u53d7\u5668\u65f6\uff0c\u653e\u5c04\u7ebf\u5c31\u4e0d\u4f1a\u589e\u52a0\u80ba\u90e8\u7684\u764c\u75c7\u8f6c\u79fb\uff1b\u8fd9\u663e\u793a\u81f3\u5c11\u5728\u90e8\u5206\u4e0a\uff0c\u80ba\u764c\u8f6c\u79fb\u662f\u8ddfTGF-β\u5728\u80bf\u7624\u7ec6\u80de\u4e0a\u7684\u76f4\u63a5\u4f5c\u7528\u6709\u5173\u7684\u3002\u8fd9\u4e9b\u6570\u636e\u542b\u793a\uff0c\u764c\u75c7\u6cbb\u7597\u6240\u4ea7\u751f\u7684TGF-β\u662f\u4e00\u79cd\u5e2e\u52a9\u764c\u75c7\u8f6c\u79fb\u7684\u8baf\u53f7\uff0c\u4e5f\u63d0\u4f9b\u4e86\u4e00\u4e2a\u539f\u7406\u6839\u636e\uff0c\u8ba9\u6211\u4eec\u5f97\u5728\u764c\u75c7\u6cbb\u7597\u65f6\u540c\u65f6\u4f7f\u7528TGF-β\u6291\u5236\u5242\u3002<\/p>\n
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\u8bd1\u6ce81\uff1a\u6b64\u4e3a\u653e\u5c04\u6027\u6cbb\u7597\u3002 \u8bd1\u6ce82\uff1a\u6b64\u4e3a\u4e00\u764c\u75c7\u5316\u5b66\u6cbb\u7597\u5e38\u7528\u836f\u7269\uff0c\u4fd7\u79f0\u300c\u5c0f\u7ea2\u8393\u300d\u3002 \u8bd1\u6ce83\uff1a\u6b64\u4e3a\u611f\u67d3\u6b64\u75c5\u6bd2\u4e4b\u521d\u671f\u7684\u4ea7\u751f\u7684\u4e09\u79cdT\u6297\u539f\u4e2d\u5176\u4e2d\u4e00\u79cd\u3002 <\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u4ecb\u7ecd<\/strong><\/section>\n<\/section>\n
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\u80bf\u7624\u6210\u957f\u56e0\u5b50TGF-β\uff0c\u65e2\u662f\u4e00\u4e2a\u80bf\u7624\u6291\u5236\u57fa\u56e0\uff0c\u4e5f\u662f\u4e00\u4e2a\u80bf\u7624\u542f\u52a8\u5b50\u3002\u5f53TGF-β\u914d\u4f53(ligands)\u7ed3\u5408\u5230\u4e0e\u5176\u5bf9\u5e94\u7684\u4e1d\u80fa\u9178\/\u9165\u80fa\u9178(Ser\/Thr)\u6fc0\u9176\u8de8\u80de\u819c\u53d7\u5668\u540e\uff0c\u8fd9\u4e9b\u53d7\u5668\u63a5\u7740\u5c31\u4f1a\u78f7\u9178\u5316\u3001\u6d3b\u5316Smad\u65cf\u7684\u8baf\u606f\u4f20\u9012\u8005\u3002\u88ab\u6d3b\u5316\u4e4b\u540e\uff0cSmad 2\u3001Smad 3 \u4f1a\u4e0e Smad 4 \u7ed3\u5408\u5e76\u8fc1\u79fb\u81f3\u7ec6\u80de\u6838\u5185\uff0c\u5728\u6b64\u5904\u8c03\u63a7\u4e0e\u7ec6\u80de\u5468\u671f\u505c\u6b62(cell cycle arrest)\u3001\u7ec6\u80de\u51cb\u4ea1(apoptosis)\u76f8\u5173\u7684\u57fa\u56e0\u4e4b\u8f6c\u5f55\u3002TGF-β\u4e4b\u6240\u4ee5\u6709\u80bf\u7624\u6291\u5236\u57fa\u56e0\u4e4b\u7528\uff0c\u5373\u7cfb\u6b64\u9879\u8c03\u63a7\u4e4b\u529f\u3002\u7684\u786e\uff0c\u5728\u5185\u76ae\u7ec6\u80de\u4e0e\u57fa\u8d28\u4e2d\u7684TGF-β\u8baf\u606f\u4f20\u9012\uff0c\u82e5\u662f\u4e27\u5931\u6216\u51cf\u5f31\uff0c\u90fd\u4f1a\u8ba9\u5185\u76ae\u7ec6\u80de\u7684\u7ec6\u80de\u6076\u6027\u8f6c\u5316(transformation)\u5927\u884c\u5176\u9053\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u5df2\u6709\u7814\u7a76\u663e\u793a\uff0c\u82e5\u5c06\u663e\u6027\u4e14\u65e0\u6548\u7684TGF-β\u53d7\u5668\u5f15\u5165\u81f3\u79fb\u8f6c\u7684\u764c\u75c7\u7ec6\u80de\u4e2d\uff0c\u4ece\u4e0a\u76ae\u7ec6\u80de\u578b\u6001\u8f6c\u53d8\u6210\u95f4\u53f6\u7ec6\u80de\u578b\u6001\u7684\u8f6c\u5206\u5316(epithelial-to-mesenchymal  transdifferentiation)\u3001\u80fd\u52a8\u6027(motility)\u3001\u4fb5\u7565\u6027(invasiveness)\u3001\u4ee5\u53ca\u5b58\u6d3b\u7387(survival)\u5747\u4f1a\u53d7\u5230\u6291\u5236\u3002\u8fd9\u8bc1\u660e\u5728\u5df2\u7ecf\u5b8c\u5168\u8f6c\u5316\u7684\u7ec6\u80de\u4e2d\uff0cTGF-β\u626e\u6f14\u4e86\u4e00\u4e2a\u80bf\u7624\u542f\u52a8\u5b50\u7684\u89d2\u8272\uff08\u4e8e\u53c2\u8003\u6587\u732e4\u4e2d\u6709\u56de\u987e\uff09\u3002\u5927\u90e8\u5206\u7684\u764c\u90fd\u4fdd\u6709TGF-β\u53d7\u5668\uff0c\u5374\u4e27\u5931\u6216\u90e8\u5206\u4e27\u5931\u4e86Smad\u4f9d\u8d56\u6027\u7684\u6297\u7ec6\u80de\u5206\u88c2\u6548\u5e94(Smad-dependent antimitogenic effect)\uff1b\u540c\u65f6\uff0c\u5728\u67d0\u4e9b\u4e2a\u6848\u4e2d\uff0c\u4ed6\u4eec\u8fd8\u4f1a\u5bf9TGF-β\u6709\u6240\u53cd\u5e94\uff0c\u800c\u83b7\u5f97\u4e86\u5e2e\u52a9\u764c\u75c7\u8f6c\u79fb\u7684\u80fd\u529b\u3002\u8fdb\u800c\uff0c\u4e0d\u8bba\u764c\u75c7\u7ec6\u80de\u8fc7\u5ea6\u751f\u4ea7TGF-β\u3001\u8fc7\u5ea6\u6d3b\u5316TGF-β\uff0c\u6216\u662f\u4e24\u8005\u517c\u5907\uff0c\u90fd\u4f1a\u85c9\u7531\u65c1\u6ccc(paracrine)\u7684\u65b9\u5f0f\uff0c\u6539\u53d8\u80bf\u7624\u5468\u56f4\u7684\u5fae\u5c0f\u73af\u5883(microenvironment)\uff0c\u5e2e\u52a9\u80bf\u7624\u7684\u53d1\u751f\u3002\u8fd9\u4e9b\u8d44\u6599\u63d0\u4f9b\u4e86\u652f\u6301\u6839\u636e\uff0c\u8ba9\u6211\u4eec\u5f97\u4ee5\u8bbe\u6cd5\u963b\u65ad\u4eba\u7c7b\u764c\u75c7\u4e2d\u7684\u81ea\u6ccc\u6027(autocrine)\u6216\u65c1\u6ccc\u6027(paracrine)\u4e4bTGF-β\u8baf\u606f\u4f20\u9012\uff0c\u4ee5\u8fbe\u6cbb\u7597\u4e4b\u76ee\u7684\u3002 \u9664Smad\u65cf\u7684\u86cb\u767d\u8d28\u5916\uff0cTGF-β\u8fd8\u53ef\u4ee5\u523a\u6fc0\u6570\u79cd\u8f6c\u5316\u7684\u8baf\u606f\u4f20\u9012\u8def\u5f84\u3002\u4e4b\u524dTGF-β\u5df2\u88ab\u8bc1\u5b9e\u53ef\u4fdd\u62a4\u8f6c\u5316\u7ec6\u80de(transformed cells)\u4e0d\u53d7\u7ec6\u80de\u51cb\u4ea1\u4e4b\u5bb3\u3002\u6b64\u7c7b\u7ec6\u80de\u53cd\u5e94\u6709\u4e00\u79cd\u53ef\u80fd\u7684\u673a\u5236\uff0c\u5c31\u662fTGF-β\u8bf1\u53d1\u4e86PI3K\u548cPI3K\u7684\u6807\u7684\u7269\uff0c\u4e5f\u5c31\u662f\u4e1d\u80fa\u9178\/\u9165\u80fa\u9178\u6fc0\u9176 Akt\uff0c\u6b64\u8baf\u606f\u4f20\u9012\u7a0b\u5e8f\u548c\u5bf9\u4e8e\u764c\u75c7\u836f\u7269\u7684\u6297\u836f\u6027\u662f\u76f8\u5173\u8fde\u7684\u3002\u6709\u4e9b\u5bf9\u4f20\u7edf\u5316\u5b66\u7597\u6cd5\u6709\u6297\u836f\u6027\u7684\u80bf\u7624\u4f1a\u8fc7\u5ea6\u8868\u73b0TGF-β\uff0c\u800cTGF-β\u7684\u6291\u5236\u5242\u7ecf\u8bc1\u660e\u53ef\u9006\u8f6c\u6b64\u79cd\u6297\u836f\u6027\u3002\u8fd8\u6709\uff0c\u5927\u90e8\u5206\u7684\u80bf\u7624\u90fd\u4f1a\u8fc7\u5ea6\u8868\u73b0TGF-β\u914d\u4f53(ligands)\u3002\u5728\u80bf\u7624\u7ec4\u7ec7\u4e0e\u5728\u8840\u6e05\u4e2d\u7684\u9ad8\u91cfTGF-β\u914d\u4f53\uff0c\u4e0e\u80bf\u7624\u8f6c\u79fb\u7684\u590d\u53d1\u3001\u60a3\u8005\u8f83\u5dee\u7684\u6108\u540e\uff0c\u5747\u6709\u6240\u76f8\u5173\u3002 \u5728\u4e73\u764c\u7684\u57fa\u56e0\u8f6c\u6b96\u6a21\u578b\u4e2d\uff0cTGF-β\u4e4b\u8baf\u606f\u4f20\u9012\u53ef\u52a0\u5f3a\u8f6c\u79fb\u65e2\u5b58\u7684\u4e73\u817a\u80bf\u7624\u3002\u8fd9\u662f\u53d7\u4f8b\u5982Neu\/ErbB2\u6216\u591a\u817a\u7624\u75c5\u6bd2\u4e2d\u592e\uff34\u6297\u539f(polyomavirus middle T antigen,PyVmT)\u7b49\u7684\u764c\u75c7\u57fa\u56e0\u4e4b\u8bf1\u53d1\u6240\u81f4\u3002\u518d\u8005\uff0c\u5728MMTV\/LTR\u4e73\u817a\u542f\u52a8\u5b50\u7684\u63a7\u5236\u4e0b\uff0c\u8868\u73b0PyVmT\u764c\u75c7\u57fa\u56e0\u7684\u57fa\u56e0\u8f6c\u6b96\u9f20\uff0c\u7ecf\u8fc7\u6709\u6761\u4ef6\u7684<\/strong>TGF-β1<\/strong>\u8bf1\u5bfc\uff0c\u53ea\u8981\u4e24\u4e2a\u793c\u62dc\u4e4b\u77ed\uff0c\u8f6c\u79fb\u80ba\u764c\u7684\u673a\u7387\u4fbf\u9ad8\u4e86\u5341\u500d<\/strong>\u3002\u6709\u4e9b\u764c\u75c7\u6cbb\u7597\u5df2\u88ab\u8bc1\u5b9e\u4f1a\u5168\u9762\u6027\u5730\u3001\u6216\u7559\u5728\u539f\u5904\u8bf1\u53d1TGF-β\u3002\u6240\u4ee5\u6211\u4eec\u63a8\u6d4b\uff0c\u88ab\u764c\u75c7\u6cbb\u7597\u6240\u8bf1\u53d1\u7684TGF-β\uff0c\u4f1a\u63d0\u4f9b\u5b58\u6d3b\u8baf\u606f\u7ed9\u8fd9\u4e9b\u5bf9\u5316\u7597\u6709\u6297\u836f\u6027\u7684\u80bf\u7624\u91cc\u7684\u7ec6\u80de\uff0c\u6216\u8005\u4e00\u90e8\u5206\u6b64\u79cd\u80bf\u7624\u4e2d\u7684\u7ec6\u80de\uff0c\u4f7f\u5b83\u4eec\u53ef\u80fd\u5728\u6cbb\u7597\u4e4b\u540e\uff0c\u7acb\u5373\u52a0\u901f\u80bf\u7624\u7684\u6269\u5c55\u3002\u5728\u6b64\uff0c\u6211\u4eec\u4f7f\u7528\u4e86\u4e73\u764c\u8f6c\u79fb\u7684MMTV\/PyVmT \u57fa\u56e0\u8f6c\u6b96\u6a21\u578b\u6765\u5c55\u793a\uff0c\u6e38\u79bb\u8f90\u5c04(ionizing radiation)\u548c\u5c0f\u7ea2\u8393(doxorubicin)\u63d0\u9ad8\u4e86\u5faa\u73af\u4e2d\u7684TGF-β1\u6d53\u5ea6\u3001\u5faa\u73af\u4e2d\u7684\u80bf\u7624\u7ec6\u80de\u6570\u3001\u4ee5\u53ca\u80ba\u90e8\u7684\u764c\u75c7\u8f6c\u79fb\u3002\u8fd9\u4e9b\u6548\u5e94\u90fd\u85c9\u7531TGF-β\u4e2d\u548c\u6297\u4f53\u7684\u65bd\u52a0\uff0c\u800c\u5f97\u4ee5\u62b5\u9500\u3002\u5728\u7f3a\u4e4f\u7b2c\u4e8c\u578bTGF-β\u53d7\u5668(TβRII)\u7684\u8001\u9f20\u8eab\u4e0a\uff0c\u653e\u5c04\u7ebf\u5219\u6ca1\u6709\u589e\u52a0\u80ba\u90e8\u7684\u764c\u75c7\u8f6c\u79fb\u3002\u8fd9\u4e9b\u8d44\u6599\u6697\u793a\uff0c\u764c\u75c7\u6cbb\u7597\u6240\u4ea7\u751f\u7684TGF-β\u662f\u80bf\u7624\u4e2d\u4e00\u4e2a\u5e2e\u52a9\u764c\u75c7\u8f6c\u79fb\u7684\u8baf\u53f7\uff0c\u56e0\u6b64\u4e5f\u63d0\u4f9b\u4e86\u539f\u7406\u6839\u636e\uff0c\u4f7f\u6211\u4eec\u5728\u4f7f\u7528\u8fd9\u4e9b\u7597\u6cd5\u65f6\uff0c\u5f97\u4ee5\u540c\u65f6\u642d\u914d\u4f7f\u7528TGF-β\u7684\u6291\u5236\u5242\u3002 <\/section>\n<\/section>\n<\/section>\n<\/section>\n
\n
\n
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\u7ed3\u679c<\/strong><\/section>\n<\/section>\n
\n
\u80f8\u8154\u653e\u5c04\u7ebf\u5904\u7406\u4e0e\u5316\u5b66\u6cbb\u7597\u63d0\u9ad8\u4e86\u5faa\u73af\u4e2d\u7684<\/strong>TGF-β<\/strong>\u91cf\u3002<\/strong>\u6211\u4eec\u5728\u516b\u5468\u5927\u7684\u672a\u4ea4\u914d\u6bcd\u9f20\u4e4b\u80f8\u8154\u4e0e\u9aa8\u76c6\u5185\uff0c\u65bd\u52a0\u4e8610 Gy\u7684\u653e\u5c04\u7ebf\u3002\u5728\u65bd\u52a0\u653e\u5c04\u7ebf\u4e4b\u540e\u969424\u5c0f\u65f6\uff0c\u8fdb\u884c\u8840\u6db2\u91c7\u96c6\u3002\u6211\u4eec\u5728\u53d7\u653e\u5c04\u5904\u7406\u4e4b\u8001\u9f20\u7684\u8840\u6d46\u91cc\uff0c\u89c2\u5bdf\u5230\u7ea6\u4e3a\u63a7\u5236\u7ec42\u500d\u7684TGF-β1\u542b\u91cf \uff08\u80f8\u8154\uff0cP=0.03\uff1b\u9aa8\u76c6\uff0cP=0.02\uff1b\u56fe\u4e00A\uff09\uff1b\u540c\u65f6\uff0cTGF-β2\u7684\u91cf\u6ca1\u6709\u6539\u53d8\uff08\u8d44\u6599\u672a\u5448\u73b0\uff09\u3002\u5728\u516b\u5468\u5927\u7684MMTV\/PyVmT\u57fa\u56e0\u8f6c\u6b96\u9f20\u4e2d\uff0c\u6216\u662f\u5728\u79cd\u4e0bMMTV\/PyVmT\u80bf\u7624\u7ec6\u80de\u3001\u7a33\u5b9a\u5730\u8f6c\u67d3\u4e86luciferase \u8868\u73b0\u8f7d\u4f53\u7684\u975e\u57fa\u56e0\u8f6c\u6b96\u9f20\u4e2d\uff0c\u6211\u4eec\u90fd\u5f97\u5230\u7c7b\u4f3c\u7684\u7ed3\u679c\uff08\u5206\u522b\u4e3aP=0.015\u4e0eP=0.007\uff0c\u76f8\u8f83\u4e8e\u63a7\u5236\u7ec4\uff0c\u56fe\u4e00B\uff09\u3002\u5728\u7ecf\u8fc7\u653e\u5c04\u5904\u7406\u540e\uff0cTGF-β1\u7684\u6d53\u5ea6\u6709\u6301\u7eed\u4e03\u5929\u6bd4\u63a7\u5236\u7ec4\u9ad8\uff08\u8d44\u6599\u672a\u5448\u73b0\uff09\u3002\u4e3a\u4e86\u5c06\u8fd9\u4e9b\u7ed3\u679c\u63a8\u5e7f\u5230\u5176\u4ed6\u7684\u764c\u75c7\u6cbb\u7597\u6cd5\uff0c\u6211\u4eec\u6d4b\u8bd5\u4e86DNA\u5d4c\u5165\u5242(DNA-intercalating agent)\u4e0etopoisomerase II\u4e4b\u6291\u5236\u5242 doxorubicin\uff08Adriamycin\uff09\u7684\u6548\u679c\u5982\u4f55\u3002\u4ece\u7b2c\u516b\u5468\u5f00\u59cb\uff0c\u57fa\u56e0\u8f6c\u6b96\u9f20\u88ab\u65bd\u884c\u4e09\u6b21\u8179\u8154\u6ce8\u5c04doxorubicin (5 mg\/kg i.p.)\uff0c\u6bcf\u6b21\u5206\u522b\u95f4\u969421\u5929\u3002\u5728\u7b2c\u5341\u4e94\u5468\u6536\u96c6\u5230\u7684\u8840\u6d46\u91cc\u53d1\u73b0\uff0c\u76f8\u8f83\u4e8e\u672a\u5904\u7406\u7684\u8001\u9f20\uff0cTGF-β1\u6d53\u5ea6\u63d0\u9ad8\u4e86\u4e24\u500d(P = 0.009\uff1b\u56fe\u4e00C)\uff0c\u800cTGF-β2\u6d53\u5ea6\u5219\u662f\u6301\u5e73\u4e0d\u53d8\u3002\u4e3a\u4e86\u8981\u6d4b\u91cf\u5728\u653e\u5c04\u5904\u7406\u540e\u4e94\u5468\u6240\u53d6\u5f97\u7684\u80ba\u810f\u7ec4\u7ec7\u4e2d\uff0c\u88ab\u6d3b\u5316\u7684TGF-β1\u4e4b\u6d53\u5ea6\uff0c\u6211\u4eec\u4f7f\u7528\u4e86\u4e00\u79cdTGF-β1\u751f\u7269\u68c0\u9a8c\u6765\u68c0\u6d4b\uff0c\u8fd9\u68c0\u6d4b\u662f\u4f7f\u7528\u4e00\u79cd\u4f1a\u7a33\u5b9a\u8868\u73b0plasminogen activator inhibitor-1\/luciferase reporter (PAI-1\/luciferase reporter) \u7684\u8c82\u80ba\u5185\u76ae\u7ec6\u80de\u6765\u8fd0\u4f5c\u7684\u3002\u76f8\u8f83\u4e8e\u672a\u53d7\u653e\u5c04\u5904\u7406\u4e4b\u8001\u9f20\u80ba\u7ec4\u7ec7\u88c2\u89e3\u6db2\uff0c\u7ecf\u8fc7\u653e\u5c04\u7ebf\u5904\u7406\u7684\u8001\u9f20\u80ba\u7ec4\u7ec7\u88c2\u89e3\u6db2\uff0c\u8bf1\u5bfc\u63d0\u5347\u4e86\u67092\u500d\u591a\u7684TGF-β1\u6d53\u5ea6\uff08P=0.0008\uff1b\u56fe\u4e00D\uff09\u3002 \u80f8\u8154\u7684\u653e\u5c04\u7ebf\u5904\u7406\u53ca\u5316\u5b66\u6cbb\u7597\uff0c\u4f1a\u589e\u52a0\u5faa\u73af\u4e2d\u7684\u80bf\u7624\u7ec6\u80de\u91cf\u4e0e\u589e\u52a0\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u3002<\/strong>TGF-β\u589e\u5f3a\u4e86\u4f1a\u8868\u73b0PyVmT\u80bf\u7624\u57fa\u56e0\u4e4b\u80bf\u7624\u7ec6\u80de\u7684\u5b58\u6d3b\u7387\uff0c\u800c\u4e14\u4e4b\u524d\u5df2\u88ab\u8bc1\u5b9e\uff0cTGF-β\u6709\u6761\u4ef6\u5730\u88ab\u8bf1\u53d1\u540e\uff0c\u4f1a\u5728MMTV\/PyVmT\u57fa\u56e0\u8f6c\u6b96\u9f20\u4e2d\u52a0\u901f\u4e73\u817a\u80bf\u7624\u7684\u8f6c\u79fb\u3002\u56e0\u6b64\uff0c\u6211\u4eec\u63a8\u6d4b\uff0c\u56e0\u6cbb\u7597\u800c\u63d0\u5347\u7684\u5faa\u73af\u4e2dTGF-β1\u6d53\u5ea6\uff0c\u53ef\u80fd\u548c\u8fd9\u4e2a\u4e73\u764c\u8f6c\u79fb\u6a21\u578b\u4e2d\u7684\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u589e\u52a0\u3001\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u589e\u52a0\uff0c\u6709\u6240\u5173\u8fde\u3002\u5e26\u6709\u80bf\u7624\u7684MMTV\/PyVmT\u8001\u9f20\u5728\u7b2c\u516b\u5468\u5927\u65f6\uff0c\u88ab\u65bd\u884c\u80f8\u8154\u653e\u5c04\u5904\u7406(thoracic irradiation)(10 Gy)\u76f4\u81f3\u7b2c\u5341\u4e09\u5468\u4e3a\u6b62\u3002\u5b9e\u9a8c\u7ec8\u7ed3\u65f6\u8fdb\u884c\u5fc3\u810f\u7a7f\u523a\u4ee5\u53d6\u5f97\u8840\u6db2\uff0c\u800c\u8840\u6db2\u4e2d\u7684\u7ec6\u80de\u90e8\u5206\uff0c\u5219\u62ff\u53bb\u6d4b\u8bd5\u5176\u5728\u6d3b\u4f53\u5916\u751f\u6210\u7ec6\u80de\u96c6\u843d\u4e4b\u80fd\u529b\u3002\u4ece\u672a\u7ecf\u653e\u5c04\u5904\u7406\u4e4b\u8001\u9f20\u6240\u53d6\u5f97\u4e4b\u8840\u6db2\uff0c\u4ea7\u751f\u4e86\u5e73\u57471.6 ± 1.5\u4e2a\u7ec6\u80de\u96c6\u843d\uff1b\u800c\u4ece\u7ecf\u8fc7\u653e\u5c04\u5904\u7406\u4e4b\u8001\u9f20\u6240\u53d6\u5f97\u4e4b\u8840\u6db2\uff0c\u4e8e10-12\u5929\u540e\u6240\u6d4b\u91cf\u7684\u7ed3\u679c\u662f\uff0c\u4ea7\u751f\u4e86\u5e73\u574728.3 ± 7.6\u4e2a\u7ec6\u80de\u96c6\u843d\uff08P=0.02\uff1a\u56fe\u4e8cA\uff09\u3002PyVmT\u6297\u4f53\u7684\u514d\u75ab\u67d3\u8272\u8bc1\u5b9e\uff0c\u8fd9\u4e9b\u751f\u957f\u7684\u7ec6\u80de\u96c6\u843d\u6709\u8868\u73b0\u764c\u75c7\u57fa\u56e0\uff08\u56fe\u4e8cA\uff09\u3002\u5faa\u73af\u4e2d\u7684\u6d3b\u80bf\u7624\u7ec6\u80de\u6570\u6709\u6240\u589e\u52a0\uff1b\u800c\u548c\u6b64\u76f8\u7b26\u5408\u7684\u662f\uff0c\u6211\u4eec\u5728\u7ecf\u653e\u5c04\u5904\u7406\u7684\u8001\u9f20\u4e2d\uff0c\u89c2\u5bdf\u5230\u8f83\u672a\u7ecf\u5904\u7406\u4e4b\u63a7\u5236\u7ec417\u500d\u7684\u80ba\u90e8\u8868\u9762\u764c\u75c7\u8f6c\u79fb\uff08P = 0.009\uff1b\u56fe\u4e8cB\uff09\u3002\u5728\u88ab\u7528doxorubicin\u5904\u7406\u76f8\u8f83\u4e8e\u672a\u5904\u7406\u4e4b\u8001\u9f20\u4e2d\uff0c\u4e5f\u5728\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u89c2\u5bdf\u5230\u7c7b\u4f3c\u7684\u4e0a\u5347\u60c5\u5f62\uff08P = 0.032\uff1b\u56fe\u4e8cC\uff09\u3002\u5728\u65bd\u52a0doxorubicin 24\u5c0f\u65f6\u4e4b\u540e\uff0c\u76f8\u8f83\u4e8e\u672a\u7ecf\u5904\u7406\u4e4b\u63a7\u5236\u7ec4\u8001\u9f20\u6240\u53d6\u5f97\u4e4b\u8840\u6db2\uff0c\u4e5f\u89c2\u5bdf\u5230\u5728\u7ec6\u80de\u7fa4\u843d\u6570\u76ee\u7684\u4e0a\u5347\uff0817.2 ± 3.7\u4e0e7.2 ± 2 colonies; n <\/em>= 5; P <\/em>= 0.007)\u3002\u4ece\u8001\u9f20\u7684\u4f53\u91cd\u53ca\u4e00\u7cfb\u5217\u7684\u80bf\u7624\u76f4\u5f84\u6570\u636e\u6765\u770b\uff0c\u53d7\u5904\u7406\u4e0e\u672a\u5904\u7406\u7684\u8001\u9f20\u5728\u80bf\u7624\u8d1f\u8377\u91cf\u4e0a\u5e76\u65e0\u5dee\u5f02\uff0c\u8fd9\u8868\u793aTGF-β1\u6d53\u5ea6\u4e4b\u5dee\u522b\uff0c\u4e0d\u80fd\u7b80\u5355\u5730\u4ee5\u80bf\u7624\u8d1f\u8377\u91cf\u4f1a\u968f\u65f6\u95f4\u589e\u52a0\u6765\u89e3\u91ca\u3002 \u63a5\u4e0b\u6765\uff0c\u6211\u4eec\u68c0\u9a8c\u4e86\u653e\u5c04\u7ebf\u6240\u8bf1\u53d1\u4e4b\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\uff0c\u662f\u5426\u4ec5\u9650\u4e8e\u5e26\u6709\u80bf\u7624\u7684MMTV\/PyVmT\u57fa\u56e0\u8f6c\u6b96\u9f20\u8eab\u4e0a\u3002\u4e3a\u4e86\u6d4b\u8bd5\u8fd9\u4e2a\u53ef\u80fd\u6027\uff0c\u6211\u4eec\u4ece\u4f1a\u8868\u73b0PyVmT\u4e4b\u57fa\u56e0\u8f6c\u6b96\u7684\u4e73\u817a\u764c\u4e2d\uff0c\u53d6\u5f97\u8868\u73b0luciferase\u7684\u80bf\u7624\u7ec6\u80de\uff0c\u7136\u540e\u5c06\u5176\u6ce8\u5c04\u81f3\u975e\u57fa\u56e0\u8f6c\u6b96\u7684\u540c\u6e90FVB\u8001\u9f20\u8eab\u4e0a\u3002\u8fd9\u4e9b\u8001\u9f20\u4e2d\u7684\u80bf\u7624\uff0c\u751f\u957f\u5728\u5de6\u4fa7\u9f20\u8e4a(inguinal)\uff08\u56db\u53f7\uff09\u7684\u4e73\u817a\u8102\u80aa\u57ab\uff0c\u6211\u4eec\u4ee5\u751f\u7269\u53d1\u5149\u6cd5\uff0c\u89c2\u5bdf\u5e76\u4f30\u8ba1\u4e86\u5176\u8f6c\u79fb\u6269\u6563\u81f3\u80ba\u810f\u7684\u60c5\u5f62\uff08\u56fe\u4e09A\uff09\u3002\u5f53\u80bf\u7624\u957f\u5230\u4e86200mm3<\/sup>\u6216\u66f4\u5927\u65f6\uff0c\u8001\u9f20\u5728\u80f8\u8154\u65bd\u52a0\u4e8610 Gy \u7684\u653e\u5c04\u7ebf\u5e76\u5728\u5176\u4f59\u90e8\u5206\u65bd\u52a0\u5c4f\u969c\uff0c\u4e24\u5468\u540e\u5c06\u8001\u9f20\u727a\u7272\u3002\u76f8\u8f83\u4e8e\u63a7\u5236\u7ec4\uff0c\u63a5\u53d7\u653e\u5c04\u5904\u7406\u7684\u8001\u9f20\u589e\u52a0\u4e86\u4e09\u500d\u7684\u8868\u9762\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb(P = 0.005; \u56fe\u4e09\uff0cB\u548cC)\u3002\u518d\u8005\uff0c\u5728\u653e\u5c04\u5904\u7406\u540e24\u5c0f\u65f6\u4e0e\u4e24\u5468\u4e4b\u540e\uff0c\u5206\u522b\u6709\u76f8\u8f83\u4e8e\u63a7\u5236\u7ec4\u591a8\u500d\u4e0e5\u500d\u7684\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u91cf\uff08\u8868\u4e00\uff09\u3002\u5728\u5b9e\u9a8c\u7ec4\u4e0e\u63a7\u5236\u7ec4\u95f4\uff0c\u539f\u53d1\u80bf\u7624\u7684\u751f\u957f\u7387\u5e76\u65e0\u4e0d\u540c\uff08\u8d44\u6599\u672a\u5448\u73b0\uff09\u3002 \u5c06\u57f9\u517b\u4e2d\u7684PyVmT\u7ec6\u80de\u66b4\u9732\u57281.25 – 7.50 Gy\u4e0b\uff0c\u4f1a\u589e\u52a0\u5176\u4ea7\u751fTGF-β\u7684\u91cf\uff08\u56fe\u56dbA\uff09\u3002\u5728\u4ee5\u4e0a\u6240\u8ff0\u4e4b\u7814\u7a76\u8fc7\u7a0b\u4e2d\uff0c\u6709\u65e2\u6210\u4e4b\u80bf\u7624\u7684\u8001\u9f20\u624d\u4f1a\u65bd\u52a0\u653e\u5c04\u7ebf\u5904\u7406\uff1b\u5faa\u73af\u4e2dTGF-β\u6d53\u5ea6\u7684\u589e\u52a0\uff0c\u6709\u53ef\u80fd\u662f\u56e0\u4e3a\u653e\u5c04\u7ebf\u5728\u764c\u75c7\u7ec6\u80de\u4e0a\u7684\u4f5c\u7528\uff0c\u56e0\u6b64\u6211\u4eec\u60f3\u6392\u9664\u6389\u8fd9\u4e2a\u53ef\u80fd\u3002\u6211\u4eec\u5bf9\u672a\u4ea4\u914d\u7684FVB\u6bcd\u9f20\u65bd\u52a0\u4e8610 Gy\u7684\u80f8\u8154\u653e\u5c04\u3002\u5728\u653e\u5c04\u5904\u7406\u540e\u4e00\u4e2a\u5c0f\u65f6\uff0c\u6211\u4eec\u4ece\u5c3e\u90e8\u9759\u8109\u6ce8\u5165\u4e86\u8868\u73b0PyVmT \u4e14\u53d7 luciferase \u7a33\u5b9a\u8f6c\u67d3(stably transfected)\u7684\u80bf\u7624\u7ec6\u80de\u3002\u80ba\u810f\u4e2d\u7684\u80bf\u7624\u7ec6\u80de\u8d1f\u8377\u91cf(tumor cell burden)\uff0c\u662f\u5728\u80bf\u7624\u7ec6\u80de\u7684\u6ce8\u5165\u4e4b\u540e\uff0c\u4f7f\u7528\u6d3b\u4f53\u5185(in vivo)\u4e0e\u6d3b\u4f53\u5916(ex vivo)\u7684\u751f\u7269\u53d1\u5149\u6765\u76d1\u6d4b\u7684\u3002\u7ecf\u653e\u5c04\u7ebf\u5904\u7406\u7684\u8001\u9f20\u80ba\u810f\uff0c\u8868\u73b0\u4e86\u8f83\u63a7\u5236\u7ec4\u4e3a\u9ad8\u7684\u751f\u7269\u53d1\u5149\u8baf\u53f7\uff08\u56fe\u56dbB\uff09\uff0c\u6b64\u8baf\u53f7\u4e0e\u4eba\u5de5\u8ba1\u6570\u4e4b\u8868\u9762\u80ba\u764c\u8f6c\u79fb\u6570\u91cf\u662f\u76f8\u5173\u8fde\u7684\uff0c\u4ea6\u4e0e\u80ba\u810f\u91cd\u91cf\u76f8\u5173\uff08\u56fe\u56db\uff0cC\u4e0eD\uff09\u3002 TGF-β<\/strong>\u4e2d\u548c\u6297\u4f53\u963b\u65ad\u4e86\u53d7\u653e\u5c04\u7ebf\u8bf1\u5bfc\u589e\u52a0\u4e4b\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb<\/strong>\u3002\u6211\u4eec\u4f7f\u7528\u4e862G7\u4e2d\u548c\u6cdbTGF-β IgG2\u6297\u4f53 (2G7 neutralizing pan-TGF-β IgG2)\u6765\u9a8c\u8bc1\uff0c\u653e\u5c04\u7ebf\u6240\u8bf1\u5bfc\u589e\u52a0\u7684\u5faa\u73af\u4e2dTGF-β\u6d53\u5ea6\uff0c\u662f\u5426\u5728\u80ba\u764c\u8f6c\u79fb\u4e2d\u626e\u6f14\u4e00\u4e2a\u6210\u56e0\u7684\u89d2\u8272\u3002\u8fd9\u4e2a\u5355\u682a\u6297\u4f53\u963b\u65ad\u4e86\u6240\u6709\u4e09\u79cd\u54fa\u4e73\u7c7b\u6240\u5177\u6709\u7684TGF-β\u5f02\u6784\u7269\uff0c\u5e76\u4e14\u5728\u6d3b\u4f53\u4e2d\u6709\u6d3b\u6027\u3002\u516b\u5468\u5927\u7684MMTV\/PyVmT\u57fa\u56e0\u8f6c\u6b96\u9f20\uff0c\u5728\u80f8\u8154\u653e\u5c04\u5904\u7406\u76842\u5c0f\u65f6\u4e4b\u524d\uff0c\u4ee515mg\/kg \u4e4b2G7\u6216PBS\u6ce8\u5c04\u81f3\u8179\u8154\u4e2d\u3002\u8fd9\u4e9b\u5904\u7406\u6301\u7eed\u6bcf\u5468\u4e24\u6b21\uff0c\u5230\u7b2c\u5341\u4e09\u5468\u4e3a\u6b62\uff0c\u6b64\u65f6\u5c06\u8001\u9f20\u727a\u7272\u5e76\u6d4b\u91cf\u662f\u5426\u80ba\u90e8\u6709\u764c\u75c7\u8f6c\u79fb\u3002\u7136\u800c\u6709\u8da3\u7684\u662f\uff0c\u65bd\u62532G7\u5230\u672a\u7ecf\u653e\u5c04\u7ebf\u5904\u7406\u7684\u8001\u9f20\u4e2d\uff0c\u5c11\u8bb8\u589e\u52a0\u4e86\u80ba\u764c\u8f6c\u79fb\uff0c\u4f46\u5728\u7edf\u8ba1\u4e0a\u5e76\u4e0d\u663e\u8457\uff08\u56fe\u4e94A\u548cB\uff09\u3002\u5728\u4e24\u79cd\u5b9e\u9a8c\u7ec4\u522b\u4e4b\u95f4\uff0c\u5e76\u672a\u5b58\u5728\u539f\u53d1\u80bf\u7624\u7ec6\u80de\u8d1f\u8377\u91cf\u7684\u5dee\u5f02\uff08\u8d44\u6599\u672a\u5448\u73b0\uff09\u3002 \u6211\u4eec\u6536\u96c6\u4e86\u8840\u6db2\u5e76\u4f53\u5916\u57f9\u517b\u5176\u7ec6\u80de\u60ac\u6d6e\u6db2\uff0c\u4ee5\u4f30\u8ba1\u5728\u5faa\u73af\u4e2d\u7684\u80bf\u7624\u7ec6\u80de\u91cf\u3002\u4ece\u672a\u7ecf\u653e\u5c04\u5904\u7406\u4e0e\u7ecf\u8fc7\u653e\u5c04\u5904\u7406\u7684\u8001\u9f20\u8eab\u4e0a\uff0c\u8840\u6db2\u4e2d\u53d6\u5f97\u800c\u57f9\u517b\u7684\u7ec6\u80de\u7fa4\u843d\u6570\uff0c\u5747\u56e0\u65bd\u52a02G7\u800c\u663e\u8457\u5730\u51cf\u5c11\uff08\u56fe\u4e94C\uff09\u3002\u6700\u540e\uff0c\u6211\u4eec\u68c0\u9a8c\u4e86\u5728\u4f53\u5916\u6dfb\u52a02G7\u4ee5\u6291\u5236TGF-β\uff0c\u662f\u5426\u4f1a\u963b\u6b62\u8001\u9f20\u8840\u6db2\u4e2d\u53d6\u5f97\u4e4b\u80bf\u7624\u7ec6\u80de\u7fa4\u843d\u751f\u957f\u3002\u5c06\u5e26\u6709\u80bf\u7624\u3001\u7ecf\u8fc7\u653e\u5c04\u5904\u7406\u7684\u8001\u9f20\u6240\u53d6\u5f97\u4e4b\u8840\u6db2\uff0c\u63a5\u79cd\u4e8e\u542b\u67092G7\u4e0e\u4e0d\u542b\u67092G7\u7684\u73af\u5883\u4e0b\uff0c\u800c\u5728\u5341\u5929\u4e4b\u540e\u8bc4\u4f30\u5176\u96c6\u843d\u751f\u957f\u60c5\u5f62\u3002\u5c06\u7ec6\u80de\u57f9\u517b\u5728\u5b58\u67092G7\u7684\u73af\u5883\u4e0b\uff0c\u53d1\u73b0\u4f1a\u964d\u4f4e70%\u7684\u7ec6\u80de\u7fa4\u843d\u6570\uff08\u56fe\u4e94D\uff09\uff0c\u8fd9\u8868\u793a\u81ea\u6ccc\u6027\u7684(autocrine) TGF-β\u5bf9\u4e8e\u8868\u73b0PyVmT\u7684\u5faa\u73af\u4e2d\u764c\u75c7\u7ec6\u80de\uff0c\u662f\u4e00\u79cd\u5b58\u6d3b\u56e0\u5b50\u3002 \u653e\u5c04\u7ebf\u8bf1\u5bfc\u589e\u52a0\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\uff0c\u9700\u8981\u80bf\u7624\u7ec6\u80de\u5185\u7684<\/strong>TGF-β<\/strong>\u53d7\u5668<\/strong>\u3002\u4ee5\u4e0a\u63cf\u8ff0\u7684\u7ed3\u679c\u663e\u793a\uff0c\u56e0\u653e\u5c04\u7ebf\u8bf1\u5bfc\u4e4b\u5faa\u73af\u4e2dTGF-β\u6d53\u5ea6\u63d0\u5347\uff0c\u662f\u5bf9\u4e8e\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u7684\u5b58\u6d3b\u4fe1\u53f7\uff0c\u8ba9\u7ec6\u80de\u53ef\u4ee5\u79fb\u5c45\u81f3\u80ba\u810f\u3001\u5728\u80ba\u810f\u91cc\u751f\u957f\u3002\u56e0\u6b64\u6211\u4eec\u63a8\u8bba\uff0c\u85c9\u7531\u79fb\u9664\u7ec6\u80de\u5bf9\u5faa\u73af\u4e2dTGF-β\u7684\u53cd\u5e94\uff0c\u4ee5\u4f7f\u5f97TβRII \u4e0d\u5b58\u5728\u4e8eMMTV\/PyVmT\u80bf\u7624\u4e2d\uff0c\u5c31\u53ef\u4ee5\u62b5\u9500\u653e\u5c04\u5904\u7406\u5728\u764c\u75c7\u8f6c\u79fb\u4e0a\u7684\u6548\u5e94\u3002\u4e3a\u68c0\u9a8c\u6b64\u63a8\u8bba\u4e4b\u53ef\u80fd\uff0c\u6211\u4eec\u4f7f\u7528\u4e86\u8868\u73b0PyVmT\u7684\u80bf\u7624\u7ec6\u80de\uff0c\u5e76\u4e14\u7528Cre-Lox\u6280\u672f\u5c06TβRII\u6709\u6761\u4ef6\u5730\u4e8e\u7ec6\u80de\u4e2d\u79fb\u9664\u3002\u542b\u6709\u6216\u672a\u542bTGFBR2\u7684PyVmT\u8868\u73b0\u578b\u80bf\u7624\u7ec6\u80de\u682a\uff08\u5728\u6b64\u4e4b\u540e\u5c06\u79f0\u4e3aPyVmT\/TGFBR2flox\/flox<\/sup> or PyVmT\/TGFBR2KO<\/sup>\uff09\u662f\u5206\u522b\u4ecePyVmT\/TGFBR2flox\/flox<\/sup> \u53ca PyVmT\/TGFBR2KO<\/sup>\u8001\u9f20\u8eab\u4e0a\u7684\u4e73\u817a\u764c\u6240\u4ea7\u751f\u3002PyVmT\/TGFBR2flox\/flox <\/sup>\u53caPyVmT\/TGFBR2KO<\/sup>\u7ec6\u80de\u682a\u5747\u4ee5luciferase\u4e4b\u8f7d\u4f53\u7a33\u5b9a\u8f6c\u67d3\uff0c\u4e14\u7ecf\u7531\u5c3e\u90e8\u9759\u8109\u6ce8\u5c04\u5165\u516b\u5468\u5927\u3001\u672a\u4ea4\u914d\u7684FVB\u6bcd\u9f20\uff0c\u8fd9\u4e9b\u6bcd\u9f20\u6709\u4e9b\u6ca1\u6709\u7ecf\u8fc7\u653e\u5c04\u7ebf\u5904\u7406\uff0c\u6709\u4e9b\u5219\u662f\u5728\u6ce8\u5c04\u80bf\u7624\u7ec6\u80de\u4e4b\u524d1\u5c0f\u65f6\uff0c\u65bd\u52a0\u4e8610 Gy\u7684\u80f8\u8154\u653e\u5c04\u3002\u4e24\u5468\u540e\u4f30\u8ba1\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u60c5\u5f62\u3002\u5728\u88ab\u6ce8\u5c04PyVmT\/TGFBR2flox\/flox<\/sup> \u7ec6\u80de\u7684\u8001\u9f20\u91cc\uff0c\u7ecf\u653e\u5c04\u5904\u7406\u4e4b\u8001\u9f20\u76f8\u8f83\u4e8e\u63a7\u5236\u7ec4\u8001\u9f20\uff0c\u53d1\u73b0\u751f\u7269\u53d1\u5149\u8baf\u53f7\u6709\u6240\u589e\u52a0\u3001\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u589e\u52a06\u500d\uff1b\u4f46\u5982\u679c\u8001\u9f20\u4e4b\u524d\u662f\u88ab\u6ce8\u5c04\u4e0d\u542b\u6709TβRII\u7684\u7ec6\u80de\uff0c\u5728\u65bd\u52a0\u4e0e\u672a\u65bd\u52a0\u653e\u5c04\u5904\u7406\u7684\u4e24\u7ec4\u4e2d\uff0c\u4fbf\u6ca1\u6709\u5dee\u522b\uff08\u56fe\u516d\uff0cA-C\uff09\u3002PyVmT\/TGFBR2KO<\/sup> \u7684\u80bf\u7624\u7ed3\u8282\u6bd4 PyVmT\/TGFBR2flox\/flox<\/sup> \u7684\u80bf\u7624\u7ed3\u8282\u8fd8\u5927\uff0c\u6b64\u7ed3\u679c\u4e0e\u4e4b\u524d\u7684\u4e00\u9879\u62a5\u544a\u662f\u76f8\u7b26\u5408\u7684\uff0c\u4e5f\u5c31\u662f\u8bf4\uff0cPyVmT\u8868\u73b0\u578b\u4e73\u764c\u7ec6\u80de\u4e4bTβRII\u4e27\u5931\uff0c\u4f1a\u589e\u8fdb\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u7684\u751f\u957f\u3002\u7ecfPCR\u6269\u589e\u80bf\u7624\u7ec4\u7ec7\u4e2d\u53d6\u5f97\u4e4bDNA\u8bc1\u5b9e\u4e86\u5728 PyVmT\/TGFBR2KO<\/sup>\u7ec6\u80de\u4e2d\uff0c\u662f\u5b58\u5728\u57fa\u56e0\u91cd\u7ec4\u7684\uff08\u56fe\u516dD\uff09\u3002<\/p>\n

\n\t  \u8ba8 \u8bba  <\/strong><\/h4>\n

\u6211\u4eec\u5728\u57fa\u56e0\u8f6c\u6b96\u8001\u9f20\u7684\u4e73\u764c\u8f6c\u79fb\u6a21\u578b\u4e2d\uff0c\u7814\u7a76\u4e86\u764c\u75c7\u6cbb\u7597\u6240\u8bf1\u53d1\u7684TGF-β\u662f\u5426\u4f1a\u52a0\u901f\u80bf\u7624\u7684\u53d1\u751f\u3002\u5728MMTV\/PyVmT\u57fa\u56e0\u8f6c\u6b96\u9f20\u4e2d\uff0c\u5728\u80ba\u90e8\u65bd\u52a0\u6e38\u79bb\u8f90\u5c04\u6216\u662f\u4ee5doxorubicin\u5904\u7406\uff0c\u90fd\u589e\u52a0\u4e86\u5faa\u73af\u4e2d\u7684TGF-β1\u91cf\u3001\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u6570\u4ee5\u53ca\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u3002\u5faa\u73af\u4e2dTGF-β1\u6d53\u5ea6\u589e\u52a0\u3001\u4e4b\u540e\u7684\u764c\u75c7\u8f6c\u79fb\u589e\u52a0\uff0c\u5e76\u4e0d\u9700\u8981\u8001\u9f20\u5728\u65bd\u52a0\u5904\u7406\u65f6\u5c31\u62e5\u6709\u80bf\u7624\uff0c\u5c31\u5982\u540c\u6211\u4eec\u4e5f\u5728\u653e\u5c04\u5904\u7406\u540e\u624d\u65bd\u6253\u80bf\u7624\u7ec6\u80de\u7684\u8001\u9f20\u4e2d\u6240\u89c2\u5bdf\u5230\u7684\u3002TGF-β1\u4f1a\u589e\u52a0\uff0c\u5e76\u4e0d\u4ec5\u9650\u4e8e\u53d7\u5230\u80f8\u8154\u653e\u5c04\u5904\u7406\u7684\u8bf1\u5bfc\uff0c\u56e0\u4e3a\u6211\u4eec\u5728\u9aa8\u76c6\u7684\u653e\u5c04\u5904\u7406\u3001\u4ee5\u53ca\u5168\u9762\u6027\u65bd\u52a0doxorubicin\u4e0b\uff0c\u4e5f\u90fd\u89c2\u5bdf\u5230\u4e86TGF-β1\u7684\u53d7\u8bf1\u5bfc\u589e\u52a0\u3002\u5728\u653e\u5c04\u5904\u7406\u540e\uff0c\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u7684\u589e\u52a0\u4ee5\u53ca\u80bf\u7624\u8f6c\u79fb\u7684\u589e\u52a0\uff0c\u90fd\u56e0\u52302G7\u7684\u65bd\u52a0\u800c\u62b5\u9500\u3002\u91cd\u8981\u7684\u662f\uff0c\u5faa\u73af\u4e2dPyVmT\u8868\u73b0\u578b\u80bf\u7624\u7ec6\u80de\u65e0\u6cd5\u5728\u67092G7\u7684\u73af\u5883\u4e0b\u8fdb\u884c\u4f53\u5916\u57f9\u517b\uff0c\u8fd9\u4e5f\u5c31\u8868\u793a\u4e86\u81ea\u6ccc\u6027(autocrine)TGF-β\u5bf9\u8fd9\u4e9b\u7ec6\u80de\u662f\u4e00\u79cd\u5b58\u6d3b\u7684\u8baf\u53f7\u3002\u8fd9\u4e9b\u7ed3\u679c\u4e0e\u4e4b\u524d\u4e24\u9879\u7814\u7a76\u662f\u76f8\u543b\u5408\u7684\uff1b\u5728\u8fd9\u4e9b\u7814\u7a76\u4e2d\uff0c\u4ee5\u53ef\u6eb6\u6027TβRII:Fc\u878d\u5408\u86cb\u767d\u3001\u6216\u7528\u53cd\u4e49TGF-β1(antisense TGF-β1)\u7a33\u5b9a\u6027\u8f6c\u67d3\u52a0\u4ee5\u963b\u65adTGF-β\uff0c\u90fd\u6291\u5236\u4e86\u80bf\u7624\u7ec6\u80de\u7684\u80fd\u52a8\u6027\u3001\u5b58\u6d3b\u7387\u3001\u6e17\u5165(intravasation)\u4ee5\u53ca\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u3002 \u8001\u9f20\u8eab\u4e0a\u7684\u80bf\u7624\u4e0d\u542bTβRII\uff0c\u653e\u5c04\u7ebf\u4fbf\u65e0\u6cd5\u5728\u8fd9\u4e9b\u8001\u9f20\u8eab\u4e0a\u52a0\u5f3a\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u3002\u4e3a\u4e86\u5c55\u793a\u6b64\u70b9\uff0c\u6211\u4eec\u4ecePyVmT\/TGFBR2flox\/flox<\/sup> \u4e0e PyVmT\/TGFBR2KO<\/sup>\u4e4b\u8001\u9f20\u8eab\u4e0a\u65e2\u6210\u4e4b\u4e73\u817a\u80bf\u7624\uff0c\u53d6\u5f97\u7ec6\u80de\u682a\u6765\u4f7f\u7528\u3002Forrester\u7b49\u4eba\u66fe\u7ecf\u63d0\u51fa\u62a5\u544a\uff0c\u4ee5MMTV\/Cre\u8868\u73b0\u6709\u6761\u4ef6\u5730\u4f7fTGFBR2\u7f3a\u5931\u65f6\uff0c\u8fd9\u4e9bknockout PyVmT\u8868\u73b0\u578b\u7684\u80bf\u7624\u53d1\u751f\u6f5c\u4f0f\u671f\u5c31\u53d8\u77ed\u4e86\u8bb8\u591a\uff0c\u5e76\u4e14\u8868\u73b0\u51fa\u660e\u663e\u589e\u52a0\u7684\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\uff0c\u8fd9\u662f\u76f8\u8f83\u4e8ePyVmT\/TGFBR2flox\/flox<\/sup>\u578b\u7684\u80bf\u7624\u3002\u56e0\u4e3a\u6211\u4eec\u4f7f\u7528\u4e86\u9759\u8109\u6ce8\u5c04\u6cd5\uff0c\u5e76\u4e14\uff0c\u6211\u4eec\u6240\u6ce8\u5165\u7ec6\u80de\u682a\u662f\u4ece\u65e2\u6210\u4e4b\u542b\u6709TβRII\u4e0e\u672a\u542bTβRII\u7684\u80bf\u7624\u800c\u6765\uff0c\u6240\u4ee5\u6211\u4eec\u7684\u7ed3\u679c\u65e0\u6cd5\u89e3\u91caForrester\u7b49\u4eba\u6240\u62a5\u5bfc\u4e4b\u764c\u75c7\u6f5c\u4f0f\u4e0e\u8f6c\u79fb\u7684\u8868\u73b0\u3002\u5c3d\u7ba1\u6211\u4eec\u5728\u7ecf\u653e\u5c04\u5904\u7406\u7684\u8001\u9f20\u4e2d\u65e0\u6cd5\u6392\u9664TGF-β\u4e4b\u589e\u52a0\uff0c\u662f\u5426\u4f1a\u5f71\u54cd\u5bbf\u4e3b\u7684\u5fae\u73af\u5883(microenvironment)\u4e0e\/\u6216\u514d\u75ab\u7cfb\u7edf\uff0c\u5e76\u8fdb\u800c\u5e2e\u52a9\u4e86\u80bf\u7624\u8f6c\u79fb\u4e4b\u8fdb\u884c\uff0c\u6211\u4eec\u4e0d\u542b\u6709TβRII\u4e4b\u80bf\u7624\u7684\u7ed3\u679c\u5374\u5f3a\u70c8\u5730\u663e\u793a\uff0c\u764c\u75c7\u8f6c\u79fb\u4e4b\u589e\u52a0\u81f3\u5c11\u5728\u90e8\u5206\u4e0a\uff0c\u662f\u8087\u56e0\u4e8eTGF-β\u5728\u764c\u75c7\u7ec6\u80de\u7684\u76f4\u63a5\u4f5c\u7528\u3002 \u5728\u80bf\u7624\u7ec6\u80de\u4e2d\uff0c\u8fd9\u4e9b\u6f5c\u5728\u53d7\u5faa\u73af\u4e2dTGF-β\u6d53\u5ea6\u8c03\u63a7\u7684\u8baf\u53f7\u53cd\u5e94\uff0c\u76ee\u524d\u4ecd\u5c5e\u672a\u660e\u3002\u7136\u800c\uff0cTGF-β\u7684\u52a9\u764c\u8f6c\u79fb\u6548\u5e94\u5e76\u4e0d\u4ec5\u9650\u4e8e\u6b64\u57fa\u56e0\u8f6c\u6b96\u6a21\u578b\u3002\u4e3e\u4f8b\u8bf4\u660e\uff0c\u5728MMTV\/LTR\u542f\u52a8\u5b50\u63a7\u5236\u4e0b\u8868\u73b0\u6709\u6d3b\u6027\u7684TGF-β1\u4e0eNeu\u7684\u53cc\u57fa\u56e0\u578b(bigenic)\u7684\u8001\u9f20\uff0c\u4e5f\u8868\u73b0\u51fa\u6bd4MMTV\/Neu\u66f4\u591a\u7684\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u4e0e\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u3002\u4f1a\u8868\u73b0Neu\u548c\u5177\u6d3b\u6027\u7684TGF-β1\u4e4b\u4e73\u817a\u80bf\u7624\u7ec6\u80de\uff0c\u80fd\u4fb5\u5165Matrigel\u5e76\u4e14\u80fd\u5728transwells\u4e0a\u79fb\u52a8\uff0c\u4f46\u5374\u53d7\u53ef\u6eb6\u6027\u7684TβRII:Fc\u7ed9\u963b\u65ad\uff0c\u8868\u793a\u5355\u5355Neu\u4e0d\u8db3\u4ee5\u8bf1\u5bfc\u51fa\u4e00\u79cd\u4fb5\u7565\u6027\u7684\u8868\u73b0\u578b\u3002\u518d\u8005\uff0c\u5728\u4f1a\u8868\u73b0\u5177\u6d3b\u6027Neu\u7684\u57fa\u56e0\u8f6c\u6b96\u80bf\u7624\u91cc\uff0c\u82e5\u5171\u540c\u8868\u73b0\u5177\u6d3b\u6027\u7684\u7a81\u53d8\u79cdAlk5\u548cTβRI\uff0c\u4f1a\u589e\u52a0\u80ba\u90e8\u8840\u7ba1\u5916\u7684\u764c\u75c7\u79fb\u8f6c(extravascular lung metastasis)\uff0c\u8fd9\u4e0eTGF-β\u4e4b\u6548\u5e94\u76f8\u7b26\uff1a\u4e5f\u5c31\u662f\u80bf\u7624\u5468\u56f4\u86cb\u767d\u9176\u3001\u764c\u75c7\u7ec6\u80de\u7684\u9644\u7740\u548c\u4fb5\u7565\u3002PyVmT\u662f\u4e00\u4e2a\u5f3a\u800c\u6709\u529b\u7684\u764c\u75c7\u57fa\u56e0\uff0c\u6211\u4eec\u4e5f\u5df2\u7ecf\u77e5\u9053\u5b83\u4f1a\u6d3b\u5316ErK\u548cPI3K\uff1b\u4f462G7\u7adf\u7136\u80fd\u5bf9\u5982\u6b64\u7684\u80bf\u7624\u7ec6\u80de\u5177\u5907\u6709\u6548\u7684\u6297\u80bf\u7624\u79fb\u8f6c\u6548\u679c\uff0c\u6709\u70b9\u4e0d\u7b26\u5408\u76f4\u89c9\u3002\u4f46\u662f\uff0c\u8fd9\u8868\u793aTGF-β\u53ef\u4ee5\u653e\u5927\u764c\u75c7\u57fa\u56e0\u7684\u8baf\u53f7\uff0c\u800c\u53ea\u8981\u8fd9\u8baf\u53f7\u5927\u4e8e\u67d0\u4e00\u9608\u503c\uff0c\u53ef\u4ee5\u5b8c\u5168\u5730\u4f7f\u80bf\u7624\u79fb\u8f6c\u88ab\u89c2\u5bdf\u5230\uff1b\u5e76\u4e14\uff0c\u76f8\u53cd\u5730\uff0c\u5728\u80bf\u7624\u57fa\u56e0\u5df2\u6076\u6027\u8f6c\u5316\u7684\u7ec6\u80de(oncogene-transformed cells)\u5185\u963b\u65adTGF-β\u8baf\u53f7\u65f6\uff0c\u4f1a\u628a\u8fd9\u4e9b\u8baf\u53f7\u964d\u4f4e\u81f3\u6bd4\u9608\u503c\u66f4\u4f4e\u7684\u7a0b\u5ea6\uff0c\u4f7f\u5176\u65e0\u6cd5\u5230\u8fbe\u764c\u75c7\u57fa\u56e0\u8bf1\u5bfc\u764c\u75c7\u8fdb\u884c\u3002\u786e\u5b9e\u5982\u6b64\uff0c\u5728\u9cde\u72b6\u7ec6\u80de\u764c(squamous cancers)\u4e2d\u88ab\u903c\u7740\u8868\u73b0\u7684\u663e\u6027-\u5177\u6d3b\u6027Smad2\uff0c\u5df2\u7ecf\u88ab\u8bc1\u5b9e\u4f1a\u548c\u6709\u6d3b\u6027\u7684Ras\u5171\u540c\u4f5c\u7528\uff0c\u4f7f\u4e0d\u5177\u4fb5\u7565\u6027\u7684\u80bf\u7624\u8f6c\u53d8\u6210\u4f1a\u8f6c\u79fb\u7684\u80bf\u7624\uff1b\u4f46Smad\u7a81\u53d8\u578b\u4e0d\u4e0eTβRI\u7ed3\u5408\uff0c\u5e76\u4f1a\u6291\u5236\u4e73\u764c\u7ec6\u80de\u7684\u8f6c\u79fb\u3002\u6700\u540e\uff0c\u5728Ras\u7ecf\u6076\u6027\u8f6c\u5316\u7684\u7ec6\u80de\u4e2d\uff0c\u663e\u6027-\u4e0d\u5177\u6d3b\u6027\u4e14\u88ab\u622a\u77ed\u7684TβRI\u8868\u73b0\u4e4b\u540e\uff0c\u5219\u662f\u4f1a\u6291\u5236\u80bf\u7624\u7684\u4ea7\u751f\u80fd\u529b(tumorigenicity)\u4ee5\u53ca\u764c\u75c7\u79fb\u8f6c\u3002 \u764c\u75c7\u6cbb\u7597\u540e\u7684\u80bf\u7624\u518d\u589e\u6b96(repopulation)\u4e0e\u53d1\u5c55\uff0c\u662f\u4e00\u4f17\u6240\u7686\u77e5\u7684\u73b0\u8c61\u3002\u5b83\u5df2\u88ab\u8bc1\u5b9e\u4f1a\u5728\u653e\u5c04\u6cbb\u7597\u3001\u5316\u5b66\u6cbb\u7597\u4ee5\u53ca\u624b\u672f\u6458\u9664\u540e\u53d1\u751f\u3002\uff08\u5728\u53c2\u8003\u6587\u732e37\u4e2d\u6709\u56de\u987e\uff09\u3002TGF-β\u7684\u6d53\u5ea6\u4f1a\u5bf9\u653e\u5c04\u7ebf\u6709\u6240\u53cd\u5e94\u800c\u589e\u52a0\uff0c\u4e5f\u88ab\u53d1\u73b0\u4e0e\u653e\u5c04\u6cbb\u7597\u540e\u4e4b\u80ba\u810f\u53d7\u4f24\u6709\u5173\uff0c\u8fd9\u662f\u7531\u80f6\u539f\u86cb\u767d\u6c89\u79ef\u3001\u80ba\u6ce1\u58c1\u7684\u589e\u539a\u4ee5\u53ca\u5185\u76ae\u7ec6\u80de\u53d7\u4f24\u6240\u81f4\u3002\u653e\u5c04\u7ebf\u5f15\u8d77\u7684\u80ba\u810f\u7ec4\u7ec7\u4f24\u5bb3\uff0c\u4f1a\u56e0\u4e3a\u65bd\u4ee5\u6297TGF-β\u6297\u4f53\u800c\u663e\u8457\u5730\u51cf\u5c11\u3002\u5728\u624b\u672f\u65b9\u9762\uff0c\u5df2\u7ecf\u6709\u4eba\u63d0\u51fa\uff0c\u56e0\u4e3a\u7ec4\u7ec7\u64cd\u4f5c\u4ee5\u53ca\u4f24\u53e3\u590d\u539f\u800c\u4ea7\u751f\u7684\u751f\u957f\u6fc0\u7d20\u8fc7\u91cf\u91ca\u653e\uff0c\u5305\u62ecTGF-β\u7684\u8fc7\u91cf\u91ca\u653e\uff0c\u4f1a\u7d27\u63a5\u7740\u624b\u672f\u4e4b\u540e\u4fc3\u8fdb\u764c\u75c7\u79fb\u8f6c\u3002\u786e\u5b9e\u5982\u6b64\uff0c\u624b\u672f\u4e4b\u540e\uff0c\u5faa\u73af\u4e2d\u968f\u5373\u53d1\u73b0\u4e86\u80bf\u7624\u7ec6\u80de\u7684\u5b58\u5728\uff0c\u4e5f\u53d1\u73b0\u80bf\u7624\u7ec6\u80de\u6570\u91cf\u7684\u589e\u52a0\uff1b\u800c\u4e14\u5728\u6cbb\u7597\u6027\u5207\u9664\u76f4\u80a0\u764c\u4e24\u5468\u4e4b\u540e\uff0c\u82e5\u5faa\u73af\u4e2d\u7684TGF-β\u6d53\u5ea6\u5c45\u9ad8\u4e0d\u4e0b\uff0c\u5c31\u8868\u793a\u764c\u75c7\u4f1a\u5f88\u5feb\u5730\u8f6c\u79fb\u81f3\u809d\u810f\u3002\u76f8\u53cd\u5730\uff0c\u5728\u624b\u672f\u521a\u5207\u9664\u76f4\u80a0\u80bf\u7624\u540e\uff0c\u8840\u6e05\u4e2d\u7684TGF-β\u6d53\u5ea6\u5374\u662f\u663e\u8457\u5730\u964d\u4f4e\u7684\u3002\u6700\u540e\uff0c\u4ee5\u5316\u5b66-\u653e\u5c04\u6cbb\u7597\u5904\u7406\u540e\u671f\u7684\u5934\u9888\u90e8\u764c\u75c7\uff0c\u4ee5\u53ca\u4ee5\u5316\u5b66\u6cbb\u7597\u5904\u7406\u975e\u5c0f\u578b\u7ec6\u80de\u80ba\u764c(non-small-cell lung cancers)\u7684\u60c5\u5f62\u4e0b\uff0c\u5faa\u73af\u4e2d\u7684TGF-β\u6d53\u5ea6\u5df2\u88ab\u8bc1\u5b9e\u548c\u5bf9\u6cbb\u7597\u7684\u53cd\u5e94\u76f8\u5173\u3002 \u5728\u672c\u7814\u7a76\u4e2d\uff0c\u6211\u4eec\u5c55\u793a\u4e86\u653e\u5c04\u6cbb\u7597\u4e0e\u5316\u5b66\u6cbb\u7597\u4f1a\u63d0\u5347\u5faa\u73af\u4e2d\u7684TGF-β\u6d53\u5ea6\u3001\u5faa\u73af\u4e2d\u7684\u764c\u75c7\u7ec6\u80de\u6570\u3001\u4ee5\u53ca\u764c\u75c7\u7684\u79fb\u8f6c\u3002\u8fd9\u4e9b\u6548\u5e94\u4f1a\u56e0\u4e3a\u7cfb\u7edf\u6027\u5730\u65bd\u52a02G7\u800c\u88ab\u963b\u65ad\uff0c\u56e0\u6b64\u652f\u6301TGF-β\u4e3a\u764c\u75c7\u8f6c\u79fb\u8fdb\u5c55\u4e4b\u8087\u56e0\u7684\u8bf4\u6cd5\u3002\u8fd9\u4e9b\u6570\u636e\u6709\u6570\u4e2a\u4e34\u5e8a\u4e0a\u7684\u542b\u610f\u3002\u7b2c\u4e00\uff0c\u56e0\u764c\u75c7\u6cbb\u7597\u800c\u589e\u52a0\u7684\u5faa\u73af\u4e2dTGF-β\u6d53\u5ea6\uff0c\u5e94\u8be5\u8981\u9884\u524d\u5730\u63a2\u8ba8\u4e0e\u76d1\u63a7\uff0c\u56e0\u4e3a\u5b83\u53ef\u80fd\u662f\u4e00\u79cd\u6807\u8bb0\uff0c\u4ee3\u8868\u80bf\u7624\u6ce8\u5b9a\u8981\u5728\u6cbb\u7597\u4e4b\u540e\u5feb\u901f\u5730\u589e\u957f\u3002\u7b2c\u4e8c\uff0c\u5728\u5faa\u73af\u4e2dTGF-β\u6d53\u5ea6\u5df2\u88ab\u89c2\u5bdf\u5230\u589e\u52a0\u7684\u75c5\u4eba\uff0c\u5176\u8eab\u4e0a\u5e26\u6709\u7684\u80bf\u7624\uff0c\u53ef\u80fd\u4f1a\u56e0\u6211\u4eec\u65bd\u52a0TGF-β\u6291\u5236\u5242\u800c\u52a0\u5f3a\u57fa\u672c\u7597\u7a0b\u7684\u6548\u679c\uff0c\u4e5f\u53ef\u80fd\u53ef\u4ee5\u62b5\u9500\u4e0e\u7597\u7a0b\u76f8\u5173\u7684\u6bd2\u6027\u6548\u5e94\uff0c\u4f8b\u5982\u653e\u5c04\u7ebf\u5f15\u8d77\u7684\u7ec4\u7ec7\u4f24\u5bb3\u4ee5\u53ca\u7ea4\u7ef4\u5316\u3002\u6211\u4eec\u9884\u671f\uff0c\u4ee5\u6211\u4eec\u73b0\u5b58\u7684\u65b9\u6cd5\u4ee5\u53ca\u5c1a\u5728\u4e34\u5e8a\u7814\u53d1\u4e2d\u7684\u6cbb\u7597\u7528TGF-β\u6291\u5236\u5242\uff0c\u8fd9\u4e9b\u5047\u8bf4\u5728\u4e0d\u4e45\u7684\u5c06\u6765\u53ef\u4ee5\u88ab\u8bc1\u5b9e <\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n\t\"\"<\/p>\n

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\u65b9 \u6cd5 <\/strong>  <\/section>\n<\/section>\n
\n
\u836f\u5242\u4e0e\u7ec6\u80de\u682a\u3002<\/strong>2G7\u878d\u5408\u7624\u662fB. Fendly (Genentech)\u6240\u8d60\u3002\u5b83\u662f\u5728Vanderbilt University Molecular Recognition Core facility\u88ab\u5236\u51fa\u4ee5\u53ca\u7528\u4eb2\u548c\u7eaf\u5316\u6cd5\u6240\u5f97\u5230\u7684\u3002\u91cd\u7ec4\u7684\u4eba\u7c7bTGF-β1\u4ee5\u53ca\u4e3aTGF-β1\u7528\u7684Quantikine Elisa kit\u662f\u4ece R&D Systems\u53d6\u5f97\u3002\u8868\u73b0PyVmT\u7684\u7ec6\u80de\u682a\u662f\u4eceMMTV\/PyVmT<\/em>\u57fa\u56e0\u8f6c\u6b96\u9f20\u7684\u4e73\u817a\u80bf\u7624\u4e2d\u53d6\u5f97\u3002PyVmT\/TGFBR2flox\/flox <\/sup>\u53caPyVmT\/TGFBR2KO<\/sup>\u7ec6\u80de\u682a\u662f\u5206\u522b\u4ecePyVmT\/TGFBR2flox\/flox <\/sup>\u53caPyVmT\/TGFBR2KO<\/sup>\u8001\u9f20\u7684\u4e73\u817a\u764c\u4e2d\u53d6\u5f97\u3002\u6211\u4eec\u5728\u8fd9\u4e9b\u8001\u9f20\u4e2d\u4f7f\u7528Cre\/Lox\u6280\u672f\uff0c\u6709\u6761\u4ef6\u5730\u4ece\u4e73\u817a\u4e2d\u5220\u9664\u4e86TGF-βII\u3002\u7ec6\u80de\u88ab\u57f9\u517b\u5728\u4e00\u4e2a37°C\u3001\u6e7f\u53165%\u7684\u6e29\u7bb1\u4e2d\uff0c\u5e76\u4e14\u57f9\u517b\u4e8e\u6dfb\u52a0\u4e8610% FBS(HyClone)\u7684DMEM(Cellgro; Mediatech Inc.)\u4e2d\u3002 TGF-β1<\/strong>\u7684\u751f\u7269\u68c0\u6d4b\u3002<\/strong>\u8c82\u80ba\u810f\u5185\u76ae\u62a5\u544a\u7ec6\u80de(mink lung epithelial reporter cell)\u5728PAI-1\u542f\u52a8\u5b50\u63a7\u5236\u4e0b\uff0c\u7a33\u5b9a\u5730\u8868\u73b0\u8424\u706b\u866bluciferase\u3002\u8fd9\u4e9b\u7ec6\u80de\u63a5\u79cd\u4e8e12-well \u57f9\u517b\u76bf\u4e0a (2×105<\/sup>\/well)\u5e76\u4e14\u7559\u7f6e\u8fc7\u591c\u4f9b\u5176\u8d34\u9644\u3002\u5df2\u77e5\u6d53\u5ea6\u7684\u53ef\u6eb6\u6027TGF-β1\u6216\u80ba\u810f\u7ec4\u7ec7\u7684\u7ec6\u80de\u88c2\u89e3\u6db2(250μg\/well)\u52a0\u5165\u4e86\u4e09\u6b21\uff0c\u800c\u8fd9\u4e9b\u7ec6\u80de\u88ab\u7559\u57285%\u4e8c\u6c27\u5316\u78b3\u300137°C\u7684\u73af\u5883\u4e0b\u57f9\u517b\u4e86\u53e6\u591624\u5c0f\u65f6\u3002\u5728\u6e05\u6d17\u4e4b\u540e\uff0c\u8fd9\u4e9b\u7ec6\u80de\u88ab\u6536\u53d6\u81f3200μg\/well\u7684\u88c2\u89e3\u7f13\u51b2\u6db2\u4e2d(Dual Luciferase Kit; Promega)\uff0cluciferase\u7684\u6d3b\u6027\u5219\u662f\u5728\u4f9d\u636e\u5382\u5546\u63d0\u4f9b\u7684\u5b9e\u9a8c\u6b65\u9aa4\u4e0b\u8fdb\u884c\u4e86\u6d4b\u91cf\u3002 DNA<\/strong>\u8403\u53d6\u4e0e\u805a\u5408\u9176\u8fde\u9501\u53cd\u5e94<\/strong>(PCR)<\/strong>\u3002\u4ee5\u77f3\u8721\u56fa\u5b9a\u7684\u80bf\u7624\u5207\u7247\u88ab\u53d6\u51fa\u548c\u91cd\u65b0\u6dfb\u52a0\u6c34\u5206\u3002\u8d81\u7740\u8fd8\u6f6e\u6e7f\u7684\u65f6\u5019\uff0c\u80bf\u7624\u90e8\u5206\u4ee5\u7ecf\u6d88\u6bd2\u4e4b\u5200\u7247\u522e\u53d6\u81f3\u7ecf\u6d88\u6bd2\u7684eppendorf\u7ba1\u4e2d\u3002DNA\u8403\u53d6\u662f\u4f7f\u7528Instagene (Bio-Rad)\u5e76\u4f9d\u5382\u5546\u63d0\u4f9b\u7684\u5b9e\u9a8c\u6b65\u9aa4\u6240\u5b8c\u6210\u3002DNA\u6837\u672c\u50a8\u5b58\u5728-20°C\uff0c\u9664\u975e\u8981\u53e6\u5916\u4f7f\u7528\u3002Cre\u8bf1\u5bfc\u7684PyVmT\/TGFBR2KO<\/sup>\u80bf\u7624\u91cd\u7ec4\uff0c\u662f\u7528PCR\u5f15\u5b50\u4ee5\u53ca\u524d\u8ff0\u4e4b\u53cd\u5e94\u6761\u4ef6\u4e0b\u6240\u9a8c\u8bc1\u7684\u3002 \u773c\u7a9d\u540e<\/strong>(retroorbital)<\/strong>\u8840\u6db2\u6536\u96c6\u4ee5\u53ca<\/strong>TGF-β1<\/strong>\u4e4b\u5b9a\u91cf<\/strong>\u3002\u8001\u9f20\u4ee51%-2% isofluorane\u9ebb\u9189\u3002\u8840\u6db2(\u7ea6250μl\/\u8001\u9f20)\u91c7\u96c6\u4e8e\u773c\u775b\u91cc\u7684\u7ed3\u819c\u9759\u8109\uff0c\u4f5c\u6cd5\u662f\u4f7f\u7528\u809d\u7d20\u5316\u4e4bNatelson tube (Fisher Scientific)\u7136\u540e\u518d\u79fb\u8f6c\u5230\u809d\u7d20\u5316\u7684(heparinized)\u73bb\u7483\u7ba1\u4e2d\u3002\u8840\u6d46\u7684\u5236\u5907\u662f\u4f7f\u7528Ficoll-Paque Plus (Amersham Biosciences)\u5e76\u4f9d\u7167\u5382\u5546\u4e4b\u4f7f\u7528\u8bf4\u660e\u8fdb\u884c\uff0c\u4e14\u589e\u52a0\u4e86\u4e00\u4e2a\u6b65\u9aa4\uff0c\u5373\u57284°C\u4e0b\u4ee510000g\u79bb\u5fc3\u5341\u5206\u949f\u4ee5\u9664\u53bb\u8840\u5c0f\u677f\u3002\u4e3a\u6d4b\u91cfPyVmT\u8868\u73b0\u578b\u7ec6\u80de\u4e4b\u57f9\u517b\u57fa\u4e2d\u7684TGF-β1\uff0c1 x 106<\/sup> \u7684\u7ec6\u80de\u88ab\u6d82\u5e03\u5728\u542b\u5728\u5b8c\u5168\u57f9\u517b\u57fa\u768410 mm\u76d8\u4e0a\uff0c\u5e76\u4e14\u4f9b\u5176\u8d34\u9644\u3002\u8be5\u57f9\u517b\u57fa\u5728\u9694\u5929\u88ab\u66f4\u6362\u6210\u65e0\u8840\u6e05\u4e4b\u57f9\u517b\u57fa\u3002\u9694\u591c\u57f9\u517b\u540e\uff0c\u7ec6\u80de\u88ab\u65bd\u4ee51.25-7.5 Gy\u3002\u8fc772\u5c0f\u65f6\u540e\uff0c\u57f9\u517b\u57fa\u7ecf\u6536\u96c6\u5e76\u4ee5\u5feb\u901f\u771f\u7a7a\u6cd5\u6d53\u7f29(3 ml to 500μl)\u3002\u8001\u9f20\u7684\u8840\u6d46\u548c\u53d7\u7ec6\u80de\u6761\u4ef6\u57f9\u517b\u57fa\uff08cell-conditioned medium\uff09\uff0c\u5747\u5728\u4e0b\u4e00\u6b65\u7684TGF-β1\u7684Quantikine Elisa kit (R&D Systems)\u4e2d\u63a5\u53d7\u6d4b\u8bd5\uff0c\u4f9d\u7167\u7684\u662f\u5382\u5546\u63d0\u4f9b\u7684\u5b9e\u9a8c\u6b65\u9aa4\u3002\u6807\u51c6\u66f2\u7ebf\u4ee531.5–2,000 pg\/ml\u7684\u4eba\u7c7b\u91cd\u7ec4TGF-β1\u7ed8\u51fa\u540e\uff0c\u88ab\u7528\u6765\u8ba1\u7b97TGF-β\u5728\u8001\u9f20\u8840\u6d46\u4e0e\u7ec6\u80de\u57f9\u517b\u57fa\u4e2d\u7684\u7b49\u91cf\u3002\u6bcf\u9879\u6807\u672c\u90fd\u5728\u53e6\u5916\u7684\u91cd\u5236\u5b9e\u9a8c\u4e2d\u91cd\u590d\u68c0\u9a8c\u4e86\u4e09\u6b21\u3002 TGF-β2<\/strong>\u4e4b\u5b9a\u91cf\u3002<\/strong>\u4f9d\u7167\u5382\u5546\u63d0\u4f9b\u4e4b\u5b9e\u9a8c\u6b65\u9aa4\uff0c\u5728\u9178\u6d3b\u5316\u4e4b\u540e\uff0c\u8840\u6d46\u6807\u672c\u4ee5TGF-β2 Quantikine Elisa kit (R&D Systems)\u6d4b\u8bd5\u3002\u6807\u51c6\u66f2\u7ebf\u4ee531.5–2,000 pg\/ml\u7684\u4eba\u7c7b\u91cd\u7ec4TGF-β2\u7ed8\u51fa\u540e\uff0c\u88ab\u7528\u6765\u8ba1\u7b97TGF-β2\u5728\u8001\u9f20\u8840\u6d46\u7684\u7b49\u91cf\u3002\u6bcf\u9879\u6807\u672c\u90fd\u5728\u53e6\u5916\u7684\u91cd\u5236\u5b9e\u9a8c\u4e2d\u91cd\u590d\u68c0\u9a8c\u4e86\u4e09\u6b21\u3002 \u8001\u9f20\u7684\u653e\u5c04\u5904\u7406\u3002<\/strong>MMTV\/PyVmT<\/em>\u57fa\u56e0\u8f6c\u6b96\u8001\u9f20\u6216\u6b63\u5e38\u7684FVB\u6bcd\u8001\u9f20(Harlan)\uff0c\u5728\u9ebb\u9189\u540e\u628a\u80cc\u90e8\u56fa\u5b9a\u5728\u955c\u53f0\u4e0a\u3002\u6211\u4eec\u4f7f\u7528\u4e86\u5355\u4e00\u7684\u80f8\u524d\u8f90\u5c04\u573a\uff0c\u5e76\u4f7f\u7528\u4e86\u94c5\u5757\u63a9\u62a4\u8001\u9f20\u8eab\u4f53\u7684\u5176\u4ed6\u90e8\u5206\u3002\u5728\u67d0\u4e9b\u5b9e\u9a8c\u4e2d\u5219\u662f\u4f7f\u7528\u4e86\u4e00\u4e2a\u5355\u4e00\u8179\u90e8\u8f90\u5c04\u573a\u3002\u8001\u9f20\u88ab\u65bd\u52a0300 kVp \u7684X\u5149\uff0c\u5176\u5242\u91cf\u4e3a 2.05 Gy\/min\u3002\u6240\u6709\u7684\u8001\u9f20\u90fd\u4f9d\u7167\u6b64\u6cd5\u89c4Institutional Animal Care and Use Committee of Vanderbilt University Medical Center\uff0c\u88ab\u7559\u5728\u4e00\u4e2a\u4e13\u95e8\u7684\u65e0\u75c5\u539f\u7a7a\u95f4\u4e2d\u3002\u5728\u52a8\u7269\u66b4\u9732\u5728\u653e\u5c04\u7ebf\u6216\u5176\u4ed6\u5904\u7406\u540e\uff0c\u5582\u98df\u6b63\u5e38\u98df\u7269\uff0c\u5e76\u4e14\u8be6\u7ec6\u89c2\u5bdf\u662f\u5426\u6709\u4efb\u4f55\u60c5\u7eea\u4e0d\u7a33\u7684\u8ff9\u8c61\u3002 \u5c0f\u7ea2\u8393<\/strong>(doxorubicin)<\/strong>\u7684\u5904\u7406\u3002<\/strong>53\u5929\u5927\u7684MMTV\/PyVmT\u8001\u9f20\uff0c\u7ecf\u8179\u8154\u6ce8\u5c04\u4e09\u6b21\u6eb6\u89e3\u4e8e\u98df\u76d0\u6c34\u6db2\u4e2d\u7684doxorubicin (Adriamycin; 5 mg\/kg; Sigma-Aldrich\uff09\uff0c\u6bcf\u6b21\u95f4\u969421\u5929\uff0c\u76f4\u5230\u7b2c95\u5929\u6b62\u3002\u7ecf\u65e0\u6548\u7a7a\u767d\u8bd5\u5242\u6216\u5c0f\u7ea2\u8393\u5904\u7406\u4e4b\u8001\u9f20\uff0c\u5176\u8840\u6db2\u6837\u672c\u548c\u80ba\u810f\u7ec4\u7ec7\uff0c\u90fd\u4e8e\u7b2c107\u5929\u89e3\u5256\u53d6\u5f97\u3002\u4e3a\u4e86\u8981\u68c0\u67e5\u5c0f\u7ea2\u8393\u5904\u7406\u4e4b\u540e\u7684\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\uff0c\u7ecf\u65e0\u6548\u7a7a\u767d\u8bd5\u5242\u6216\u5c0f\u7ea2\u8393\u5904\u7406\u4e4b\u8001\u9f20\uff0c\u5176\u8840\u6db2\u5728\u53d6\u5f9724\u5c0f\u65f6\u540e\uff0c\u53c8\u52a0\u5165\u4e86\u5355\u4e00\u5242\u91cf(5 mg\/kg)\u3002 \u4fa6\u6d4b\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u3002<\/strong>\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u4e4b\u57f9\u517b\u65b9\u6cd5\u5982\u524d\u8ff0\uff0c\u4ec5\u6709\u5c11\u90e8\u5206\u4e4b\u4fee\u6539\u3002\u627c\u8981\u5730\u8bf4\uff0c\u8840\u6db2\u53d6\u5f97\u4e8e\u5fc3\u810f\u7a7f\u523a\u3002\u7ec6\u80de\u60ac\u6d6e\u6db2\uff08\u5305\u62ecbuffy coat\u4ee5\u53ca\u7ea2\u8840\u7403\uff09\u4ece\u8840\u6d46\u4e2d\u5206\u79bb\u51fa\u540e\uff0c\u63a5\u79cd\u57286-well\u76d8\u4e0a\uff0c\u8fd9\u4e9b\u76d8\u4e0a\u5e03\u6709\u4e86\u751f\u957f\u6fc0\u7d20\u51cf\u91cf\u4e4bMatrigel (BD Biosciences)\uff0c\u5e76\u6dfb\u52a0\u6709DMEM\u300110%FBS\uff0c\u4e4b\u540e\u4fbf\u4e8e37°C\u30015%\u4e8c\u6c27\u5316\u78b3\u4e4b\u6e29\u7bb1\u4e2d\u57f9\u517b\u3002\u9694\u5929\uff0c\u5728\u6bcf\u4e2awell\u4f7f\u7528\u4e86\u7ea2\u8840\u7403\u79fb\u9664\u7f13\u51b2\u6db2(4.15 g NH4Cl, 0.5 g NaHCO3, 0.0186 g disodium EDTA in 200 ml water)\u4ee5\u53caPBS\uff0c\u6570\u6b21\u7f13\u548c\u7684\u51b2\u6d17\u3002DMEM\u4e0e10%FBS(3ml\/well)\u6dfb\u52a0\u540e\uff0c\u65b0\u9c9c\u7684\u57f9\u517b\u57fa\u6bcf\u4e09\u5929\u5c06\u4f1a\u8865\u5145\u4e00\u6b21\u3002\u8fc7\u4e8610-12\u5929\u540e\uff0c\u4ee5\u4eba\u5de5\u8ba1\u6570\u5927\u5c0f\u4e3a50μm\u4ee5\u4e0a\u4e4b\u7ec6\u80de\u96c6\u843d\u3002PyVmT\u8868\u73b0\u662f\u7528\u514d\u75ab\u7ec6\u80de\u5316\u5b66\u65b9\u6cd5\u6765\u4fa6\u6d4b\u7684\u3002\u627c\u8981\u5730\u8bf4\uff0c\u5438\u51fa\u57f9\u517b\u57fa\u3001\u4ee5PBS\u6e05\u6d17wells\uff0c\u7136\u540e\u7ec6\u80de\u96c6\u843d\u4ee510%\u4e2d\u6027\u7f13\u51b2\u7684\u798f\u5c14\u9a6c\u6797(formalin)\uff0c\u5728\u5ba4\u6e29\u4e0b\u56fa\u5b9a30\u5206\u949f\uff0c\u518d\u7528PBS\u6e05\u6d172\u6b21\uff0c\u518d\u4e8e\u5ba4\u6e29\u4e0b\u4e0ePBS\u4e2d\u4e4b3%BSA\u5171\u5b581\u5c0f\u65f6\u3002\u57f9\u517b\u76d8\u63a5\u7740\u57f9\u517b\u9694\u591c\uff0c\u4e8e4°C\u7f6e\u653e\u4e8e\u542b\u6709\u751f\u7269\u7d20\u6807\u8bb0\u7684\u6297PyVmT\u7684\u8001\u9f20\u5355\u682a\u6297\u4f53(diluted 1:500, BIOT-115L; Covance)\u3002\u7136\u540e\uff0c\u52a0\u5165\u4e0estreptavidin\u7ed3\u5408\u4e4b\u8367\u5149\u4e8c\u7ea7\u6297\u4f53(Oregon Green 488; Invitrogen) \u5ba4\u6e29\u4e0b1\u5c0f\u65f6\uff0c\u4e4b\u540e\u4f7f\u7528Hoechst \u7ec6\u80de\u6838\u67d3\u8272\u6cd5(1 μg\/ml \u5341\u4f7f\u7528\u5206\u949f)\u3002\u514d\u75ab\u8367\u5149\u662f\u4ee5Leica DM IRB \u5012\u7f6e\u663e\u5fae\u955c\u6240\u89c2\u5bdf\u7684\u3002 \u751f\u4ea7\u53cd\u8f6c\u5f55\u75c5\u6bd2\u8f7d\u4f53\u4ee5\u53ca\u7ec6\u80de\u8f6c\u5bfc\u3002<\/strong>MMTV\/PyVmT\u7ec6\u80de\uff0c\u662f\u4ee5luciferase\u4e4b\u8f7d\u4f53\u7a33\u5b9a\u8f6c\u67d3\u7684\u3002\u4e00\u4e2aluciferase cassette\u4ecepGL3-Basic (Promega)\u88c1\u5207\u4e0b\u6765\uff0c\u5e76\u5d4c\u5165pMSCV-puro (Clontech)\u4e4b\u591a\u91cd\u590d\u5236\u4f4d\u4e0a\u3002amphotropic packaging Phoenix cells \u8f6c\u67d3\u540e\uff0c\u4ea7\u751f\u611f\u67d3\u6027\u75c5\u6bd2\u9897\u7c92\uff0c\u5982\u524d\u8ff0\u3002\u57f9\u517b\u751f\u957f\u4e2d(subconfluent)\u4e4b\u764c\u75c7\u57fa\u56e0\u8868\u73b0\u7ec6\u80de\uff0c\u57284 μg\/ml Polybrene (Sigma-Aldrich)\u4e2d\uff0c\u4ee5\u75c5\u6bd2\u4e0a\u6e05\u6db2\u8f6c\u5bfc6\u5c0f\u65f6\uff0c\u800c\u542b\u6709\u75c5\u6bd2\u9897\u7c92\u7684\u57f9\u517b\u57fa\u57286\u5c0f\u65f6\u4e4b\u540e\u66f4\u6362\uff1b\u572848\u5c0f\u65f6\u540e\uff0c\u518d\u6dfb\u52a0\u542b\u670910%\u5df2\u7ecf\u52a0\u70ed\u53d8\u6027\u4e4bFCS\u7684DMEM\uff0c\u5e76\u4e8e7-10\u5929\u540e\u5c06\u6297\u836f\u7684\u7ec6\u80de\u96c6\u843d\u5408\u5e76\u3002 \u80bf\u7624\u4ea7\u751f\u80fd\u529b\u4ee5\u53ca\u80bf\u7624\u8f6c\u79fb\u4e4b\u7814\u7a76\u3002<\/strong>\u57281%–2% isofluorane \u4e4b\u9ebb\u9189\u4e0b\uff0cMMTV\/PyVmT\/Luc <\/em>\u7ec6\u80de(2 × 106 <\/sup>cells in 200 μl PBS) \u88ab\u6ce8\u5c04\u4e8eFVB\u6bcd\u9f20\u7684\u5de6\u4fa7\u56db\u53f7\u4e73\u817a\u8102\u80aa\u57ab\u3002\u627c\u8981\u5730\u8bf4\uff0c\u5728\u6ce8\u5165\u80bf\u7624\u7ec6\u80de\u4e4b\u524d\uff0c\u8102\u80aa\u57ab\u4fbf\u5df2\u7ecf\u4ee5\u624b\u672f\u4f7f\u5176\u66b4\u9732\u5728\u5916\uff0c\u800c\u4f24\u53e3\u4ee5\u5e72\u51c0\u5939\u5b50\u5bc6\u5408\uff0c\u5e76\u4e8e10\u5929\u4e4b\u540e\u53d6\u8d70\u3002\u6bcf\u5468\u4ee5\u751f\u7269\u53d1\u5149\u6cd5\u68c0\u67e5\u80bf\u7624\u4e24\u6b21\uff0c\u5e76\u7cfb\u5217\u5730\u4ee5\u6d4b\u5f84\u5668\u6d4b\u91cf\u4e4b\u3002\u8fd9\u4e9b\u80bf\u7624\u7684\u4ee5\u7acb\u65b9\u516c\u5398(mm3<\/sup>)\u8ba1\u7b97\u4e4b\u4f53\u79ef\uff0c\u662f\u4ee5\u6b64\u6570\u5b66\u5f0f\u8ba1\u7b97\uff1av <\/em>= (w<\/em>2 × l<\/em>)\/2\uff0cv\u4ee3\u8868\u4f53\u79ef\uff0cw\u4ee3\u8868\u5bbd\u5ea6\uff0cl\u4ee3\u8868\u957f\u5ea6\u3002\u5f53\u80bf\u7624\u8fbe\u5230\u4e86200 mm3<\/sup>\u6216\u66f4\u5927\u7684\u4f53\u79ef\uff08\u7ea6\u4e24\u5468\u65f6\u95f4\uff09\uff0c\u8001\u9f20\u5c31\u88ab\u65bd\u4ee5\u653e\u5c04\u7ebf\u5904\u7406\uff0c\u6216\u662f\u4e0d\u4f5c\u4efb\u4f55\u5904\u7406\u3002\u8001\u9f20\u7ee7\u7eed\u6bcf\u5468\u4e24\u6b21\u63a5\u53d7\u751f\u7269\u53d1\u5149\u6cd5\u7684\u76d1\u63a7\u89c2\u5bdf\uff0c\u76f4\u5230\u5b9e\u9a8c\u7ec8\u7ed3\u3002\u4e24\u5468\u4e4b\u540e\uff0c\u5c06\u8001\u9f20\u727a\u7272\u5e76\u53d6\u5f97\u57fa\u672c\u7684\u80bf\u7624\u4e0e\u80ba\u810f\u3002\u4ee5\u89e3\u5256\u663e\u5fae\u955c\u8ba1\u7b97\u80ba\u810f\u8868\u9762\u4e4b\u764c\u75c7\u8f6c\u79fb\u6570\uff0c\u4e4b\u540e\u8fd9\u4e9b\u80ba\u810f\u4ee510%\u4e2d\u6027\u7f13\u51b2\u4e4b\u798f\u5c14\u9a6c\u6797(formalin)\u56fa\u5b9a\u4e4b\u3002\u56fa\u5b9a\u597d\u7684\u80bf\u7624\u5207\u7247\uff0c\u4ee5H&E\u67d3\u8272\u4e4b\uff0c\u5e76\u4ee5\u663e\u5fae\u955c\u68c0\u67e5\u662f\u5426\u6709\u80ba\u764c\u4e4b\u8f6c\u79fb\u3002\u8840\u6db2\u662f\u7531\u5fc3\u810f\u7a7f\u523a\u53d6\u5f97\u4ee5\u5982\u524d\u8ff0\uff0c\u6d4b\u91cfTGF-β\u4e4b\u6d53\u5ea6\u4ee5\u53ca\u5faa\u73af\u4e2d\u4e4b\u80bf\u7624\u7ec6\u80de\u6570\u3002 \u5728\u5176\u4ed6\u7684\u60c5\u5f62\u91cc\uff0c\u6211\u4eec\u4f7f\u7528\u4e86MMTV\/PyVmT<\/em>\u3001<\/em>PyVmT\/TGFBR2<\/em>flox\/flox<\/sup><\/em>\u6216PyVmT\/TGFBR2<\/em>KO<\/sup><\/em>\u7ec6\u80de\u6765\u8868\u73b0luciferase\u30022.5 × 106<\/sup> \u4e4b\u5355\u4e00\u7ec6\u80de\u60ac\u6d6e\u6db2\u5236\u5907\u540e\uff0c\u91cd\u65b0\u6eb6\u4e8e\u65e0\u83cc\u4e4bPBS\u6db2\u4e2d\u30020.5 × 106 <\/sup>(in 200 μl)\u7684\u7ec6\u80de\u88ab\u6ce8\u5c04\u5165FVB\u6bcd\u9f20\u4e4b\u4fa7\u9762\u5c3e\u90e8\u9759\u8109\u4e2d\u3002\u9759\u8109\u6ce8\u5c0424\u5c0f\u65f6\u540e\uff0c\u80bf\u7624\u7ec6\u80de\u4e8e\u8001\u9f20\u80ba\u90e8\u4e4b\u4f4d\u7f6e\uff0c\u4ee5\u751f\u7269\u53d1\u5149\u6cd5\u786e\u5b9a\u4e4b\uff0c\u5e76\u4e14\u81ea\u6b64\u4e4b\u540e\u6bcf\u5468\u8ffd\u8e2a\u4e24\u6b21\u3002\u4e3a\u4e86\u8981\u5728\u6d3b\u4f53\u5185\u963b\u65adTGF-β\uff0c\u5728\u628a10 Gy\u6ce8\u5165\u8001\u9f20\u80f8\u8154\u7684\u524d24\u5c0f\u65f6\uff0c\u5c0615 mg\/kg\u76842G7\u6ce8\u5165\u8001\u9f20\u8179\u8154\u5185\uff0c\u6bcf\u5468\u4e24\u6b21\uff0c\u6301\u7eed\u8fdb\u884c\uff0c\u76f4\u5230\u8001\u9f20\u6b7b\u4ea1\u3002 \u751f\u7269\u53d1\u5149\u6cd5\u663e\u5f71\u6280\u672f\u3002<\/strong>\u8981\u5c06\u751f\u7269\u53d1\u5149\u4e4b\u8baf\u53f7\u4e0e\u80bf\u7624\u8d1f\u8f7d\u91cf\u5efa\u7acb\u5b9a\u91cf\u7684\u5bf9\u5e94\u5173\u7cfb\uff0c\u5148\u4ee5\u6eb6\u89e3\u4e8e\u53bb\u79bb\u5b50\u6c34\u7684 luciferin substrate (d-luciferin potassium salt; Promega)\u8fdb\u884c\u8179\u8154\u6ce8\u5c04(0.15 mg\/g body weight)\uff0c\u5728\u6ce8\u5c04\u4e4b\u540e12\u5206\u949f\u5185\u53d6\u5f97\u5f71\u50cf\u3002\u6839\u636e\u6211\u4eec\u4e4b\u524d\u7684\u65f6\u95f4\u8bb0\u5f55\u4e4b\u5b9e\u9a8c\uff0c\u5728\u6b64\u65f6\u95f4\u8bb0\u5f55\u8baf\u53f7\u9ad8\u5cf0\u5904\u4e4b\u5f3a\u5ea6\uff08\u8d44\u6599\u672a\u5448\u73b0\uff09\u3002\u5728\u53d6\u5f97\u5f71\u50cf\u65f6\uff0c\u5c06\u8001\u9f20\u4ee5isofluorane\u9ebb\u9189\u3002\u751f\u7269\u53d1\u5149\u663e\u5f71\u662f\u4ee5Vanderbilt University Small Animal Imaging Center\u7684 IVIS-200 \u663e\u5f71\u7cfb\u7edf (Xenogen)\u5b8c\u6210\u7684\u3002\u6211\u4eec\u91c7\u7528\u4e863-5\u5206\u949f\u7684\u6574\u5408\u8ba1\u7b97\u65f6\u95f4\uff0c\u5e76\u4f7f\u7528on-chip binning of 8\uff0c\u4ee5\u589e\u52a0\u8baf\u53f7-\u566a\u58f0\u6bd4\u3002\u751f\u7269\u53d1\u5149\u663e\u5f71\u4e4b\u5b9a\u91cf\u5206\u6790\u662f\u4ee5Living Image software (Xenogen)\u5b8c\u6210\uff0c\u6211\u4eec\u5728\u6b64\u5b9a\u4e49\u4e86\u611f\u5174\u8da3\u533a\u57df\uff08regions of interest\uff0cROI\uff09\u5e76\u6d4b\u91cf\u4e86integrated photon counts\u3002 <\/p>\n
\u7edf\u8ba1\u3002<\/strong>\u6240\u6709\u7684\u5b9e\u9a8c\u6570\u636e\u5747\u4ee5\u53cc\u5c3eStudent’s t <\/em>test\u5206\u6790\u3002P\u503c\u5c0f\u4e8e0.05\u88ab\u89c6\u4e3a\u663e\u8457\u3002<\/section>\n<\/section>\n

\"\" <\/p>\n

\u7a33\u5b9a\u8868\u73b0luciferase\u7684MMTV\/PyVmT\u7ec6\u80de\uff0c\u88ab\u6ce8\u5c04\u5165FVB\u8001\u9f20\u7684\u53f3\u4fa7\u9f20\u8e4a\u4e73\u817a\u8102\u80aa\u57ab\u4e2d\u3002\u62e5\u6709200mm3<\/sup>\u4ee5\u4e0a\u80bf\u7624\u7684\u8001\u9f20\uff0c\u4e0d\u52a0\u4ee5\u653e\u5c04\u5904\u7406\uff0c\u6216\u662f\u5728\u80f8\u8154\u65bd\u52a010 Gy\u7684\u653e\u5c04\u5904\u7406\u3002\u572824\u5c0f\u65f6\u53ca2\u5468\u540e\uff0c\u4ee5\u5fc3\u810f\u7a7f\u523a\u53d6\u5f97\u8840\u6db2\uff0c\u5e76\u6d4b\u91cf\u7ec6\u80de\u60ac\u6d6e\u6db2\u5728\u6d3b\u4f53\u5916\u5f62\u6210\u7ec6\u80de\u96c6\u843d\u7684\u80fd\u529b\uff0c\u5982\u300c\u65b9\u6cd5\u300d\u6587\u4e2d\u6240\u793a\u3002\u6570\u636e\u4e3a\u4e24\u4e2a\u5206\u522b\u7684\u5b9e\u9a8c\u4e2d\uff0c\u6bcf\u7ec4\u4e94\u53ea\u8001\u9f20\u7684\u5e73\u5747\u503c±\u6807\u51c6\u5dee\u3002RT\u662f\u6307\u653e\u5c04\u6cbb\u7597\uff08radiation therapy\uff09\u3002\u5728\u540c\u4e00\u65f6\u95f4\u70b9\u4e0b\uff0cAP <\/em>= 0.016 versus 0 Gy\u3002 \"\" \u653e\u5c04\u7ebf\u4e0e\u5316\u5b66\u6cbb\u7597\u589e\u52a0\u5faa\u73af\u4e2dTGF-β1\u6d53\u5ea6\u3002 (A<\/strong>) 10 Gy \u7684\u653e\u5c04\u7ebf\u88ab\u65bd\u52a0\u4e8eFVB\u8001\u9f20\u4e4b\u80f8\u8154(thorax) (\u5de6)\u6216\u9aa8\u76c6\u8154(pelvis )(\u53f3)\u300224\u5c0f\u65f6\u4e4b\u540e\u53d6\u5f97\u8840\u6db2\uff0c\u8840\u6d46\u4e2d\u4e4bTGF-β1\u6d53\u5ea6\u4ee5\u5728\u300c\u65b9\u6cd5\u300d\u4e2d\u6240\u8ff0\u6d4b\u91cf\u3002(B<\/strong>) \u516b\u5468\u5927\u3001\u5e26\u6709\u80bf\u7624\u4e4bMMTV\/PyVmT <\/em>\u8001\u9f20\uff0c\u6216\u975e\u57fa\u56e0\u8f6c\u6b96\u4e4bFVB \u8001\u9f20\uff0c\u5728\u56db\u53f7\u4e73\u817a\u8102\u80aa\u57ab\u5e26\u6709200mm3<\/sup>\u4ee5\u4e0a\u5927\u5c0f\u4e4b\u80bf\u7624\uff0c\u4e0d\u4f5c\u4efb\u4f55\u5904\u7406\u6216\u65bd\u52a010 Gy \u4e8e\u80f8\u8154\u3002\u8840\u6d46\u4e2dTGF-β1\u6d53\u5ea6\uff0c24\u5c0f\u65f6\u540e\u6d4b\u91cf\u4e4b\u3002(C<\/strong>) \u5728\u7b2c\u516b\u5468\u8d77\uff0c\u6bcf\u969421\u5929\uff0c\u4ee5\u7a7a\u767d\u8bd5\u5242\u6216\u8179\u8154\u6ce8\u5c04\u5c0f\u7ea2\u8393 (5 mg\/kg i.p.)\uff0c\u5904\u7406\u57fa\u56e0\u8f6c\u6b96\u8001\u9f20\u4e09\u6b21\u3002\u8840\u6d46\u4e2dTGF-β1\u6d53\u5ea6\u5728\u7b2c\u5341\u4e94\u5468\u6d4b\u91cf\u4e4b\u3002A<\/strong>–C <\/strong>\u4e4b\u6570\u636e\u4ee3\u8868\u4e09\u4e2a\u4e0d\u540c\u7684\u72ec\u7acb\u5b9e\u9a8c\uff0c\u6bcf\u7ec4\u4f7f\u7528\u4e09\u4e2a\u5b9e\u9a8c\u5bf9\u8c61\u3002(D<\/strong>) FVB\u8001\u9f20\u80f8\u8154\u88ab\u65bd\u52a010 Gy\u3002\u4e94\u5468\u540e\uff0c\u53d6\u5f97\u7ecf\u653e\u5c04\u7ebf\u5904\u7406\u3001\u63a7\u5236\u7ec4\u8001\u9f20\u4e4b\u80ba\u810f\uff0c\u53ca\u5176\u7ec6\u80de\u88c2\u89e3\u6db2(250 μg\/ml)\uff0c\u52a0\u5230\u542b\u6709\u8c82\u80ba\u4e0a\u76ae\u7ec6\u80de\u7684triplicate wells\uff0c\u8fd9\u4e9b\u7ec6\u80de\u4f1a\u7a33\u5b9a\u5730\u8868\u73b0plasminogen activator inhibitor–1\/luciferase reporter (PAI-1\/luciferase reporter)\u3002\u4e8c\u5341\u56db\u5c0f\u65f6\u540e\uff0c\u6d4b\u91cfluciferase\u4e4b\u8868\u73b0\uff0c\u65b9\u6cd5\u5982\u300c\u65b9\u6cd5\u300d\u90e8\u5206\u4e2d\u6240\u8ff0\u3002\u56fe\u793a\uff1a*\u8868\u793aP <\/em>< 0.05\uff0c **\u8868\u793aP <\/em>< 0.01\uff0c ***\u8868\u793aP <\/em>< 0.001 \u76f8\u5bf9\u4e8e\u63a7\u5236\u7ec4\u3002 \"\" \u653e\u5c04\u7ebf\u4e0e\u5316\u5b66\u6cbb\u7597\u589e\u52a0\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\u91cf\u4ee5\u53ca\u80ba\u90e8\u4e4b\u80bf\u7624\u8f6c\u79fb\u3002(A)<\/strong> MMTV\/PyVmT\u6bcd\u9f20\u5728\u516b\u5468\u5927\u65f6\uff0c\u63a5\u53d7\u80f8\u8154\u653e\u5c04\u7ebf\u5904\u7406\u3002\u5728\u7b2c\u5341\u4e09\u5468\u65f6\uff0c\u5f53\u5b9e\u9a8c\u7ec8\u7ed3\uff0c\u4ee5\u5fc3\u810f\u7a7f\u523a\u53d6\u5f97\u8840\u6db2\uff0c\u5e76\u91cf\u53d6\u5176\u7ec6\u80de\u60ac\u6d6e\u6db2\u5728\u4f53\u5916\u4ea7\u751f\u7ec6\u80de\u96c6\u843d\u4e4b\u80fd\u529b\uff0c\u5982\u300c\u65b9\u6cd5\u300d\u4e2d\u6240\u8ff0\u3002CTCs\u4ee3\u8868\u5faa\u73af\u4e2d\u80bf\u7624\u7ec6\u80de\uff08circulating tumor cells\uff09\u3002\u5728\u4e0b\u9762\u4e3a\u4e00\u4e9b\u5177\u6709\u4ee3\u8868\u6027\u7684\u5f71\u50cf\uff0c\u662f\u7531\u8840\u6db2\u4e2d\u53d6\u5f97\u3001\u5faa\u73af\u4e2d\u5355\u4e00\u4e2a\u80bf\u7624\u7ec6\u80de\u5f62\u6210\u7684\u7ec6\u80de\u96c6\u843d\u3002\u57fa\u56e0\u8f6c\u6b96\u6210\u529f\u7684\u7ec6\u80de\u96c6\u843d\uff0c\u7528PyVmT\u6297\u4f53\u548c\u8367\u5149\u4e4b\u6b21\u7ea7\u6297\u4f53\u5904\u7406\uff0c\u5e76\u4ee5\u8367\u5149\u663e\u5fae\u955c\u89c2\u5bdf\u5e76\u4f30\u8ba1\u4e4b\u3002(B<\/strong>) \u4e0eA<\/strong> \u540c\u6837\u4e4b\u8001\u9f20\uff0c\u5728\u7b2c\u5341\u4e09\u5468\u5927\u65f6\u8ba1\u7b97\u80ba\u90e8\u8868\u9762\u764c\u75c7\u4e4b\u8f6c\u79fb\u6570\u76ee\u3002A\u548cB\u4e2d\u4e4b\u6570\u636e\u662f\u4ee3\u8868\u4e09\u4e2a\u72ec\u7acb\u7684\u5b9e\u9a8c\uff0c\u6bcf\u7ec4\u4e2d\u6709\u56db\u53ea\u8001\u9f20\u3002\u4ece\u63a7\u5236\u7ec4\u4ee5\u53ca\u7ecf\u653e\u5c04\u7ebf\u5904\u7406\u4e4b\u57fa\u56e0\u8f6c\u6b96\u8001\u9f20\u4e0a\uff0c\u53d6\u5f97\u5177\u4ee3\u8868\u6027\u4e4b H&E \u67d3\u8272\u7684\u80ba\u90e8\u7ec4\u7ec7\u5207\u7247\u3002\u8fd9\u4e9b\u5207\u7247\u662f\u80f8\u8154\u653e\u5c04\u5904\u7406\u540e\u4e94\u5468\u6240\u53d6\u5f97\uff0c\u5982\u4e0b\u65b9\u6240\u793a\u3002\u9ed1\u8272\u7bad\u5934\u6240\u6307\u4e3a\u80ba\u90e8\u764c\u75c7\u8f6c\u79fb\u3002(C<\/strong>) \u516b\u5468\u5927\u3001\u5e26\u6709\u80bf\u7624\u7684 MMTV\/PyVmT <\/em>\u57fa\u56e0\u8f6c\u6b96\u8001\u9f20\uff0c\u6bcf\u969421\u5929\u4ee5\u7a7a\u767d\u8bd5\u5242\u6216\u8179\u8154\u6ce8\u5c04\u5c0f\u7ea2\u8393(5 mg\/kg i.p.)\u5904\u7406\u5171\u4e09\u6b21\u3002\u6b64\u5b9e\u9a8c\u4e8e\u7b2c\u5341\u4e94\u5468\u65f6\u7ec8\u7ed3\uff0c\u5e76\u8ba1\u7b97\u80ba\u90e8\u8868\u9762\u4e4b\u764c\u75c7\u8f6c\u79fb\u6570\u91cf\u3002\u5177\u4ee3\u8868\u6027\u4e4bH&E\u67d3\u8272\u80ba\u90e8\u5207\u7247\uff0c\u5176\u542b\u6709\u764c\u75c7\u8f6c\u79fb\u90e8\u5206\u7684\u4e2d\u5fc3\u5982\u53f3\u65b9\u56fe\u793a\u3002\u539f\u59cb\u653e\u5927\u500d\u7387\u4e3a100\u500d\u3002*\u8868\u793aP <\/em>< 0.05\uff0c **\u8868\u793aP <\/em>< 0.01 \uff0c\u76f8\u8f83\u4e8e\u63a7\u5236\u7ec4\u3002 \"\" <\/p>\n
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  \"\"   \u653e\u5c04\u7ebf\u7684\u5148\u884c\u5904\u7406\uff0c\u4f1a\u4f7f\u79fb\u8f6c\u7684\u80ba\u764c\u7ec6\u80de\u66f4\u80fd\u591f\u62d3\u5c55\u5728\u539f\u672c\u65e0\u80bf\u7624\u7684\u8001\u9f20\u8eab\u4e0a\u3002(A<\/strong>) MMTV\/PyVmT <\/em>\u7ec6\u80de\uff0c\u5728\u52a0\u6709\u4e0d\u542b\u8840\u6e05\u4e4b\u57f9\u517b\u57fa\u4e4b100-mm \u57f9\u517b\u76bf\u91cc\uff0c\u4ee51.25–7.5 Gy\u5904\u7406\u3002\u53d7\u7ec6\u80de\u6240\u5f71\u54cd\u4e4b\u57f9\u517b\u57fa\u572872\u5c0f\u65f6\u540e\u8fdb\u884c\u6536\u96c6\uff0c\u5e76\u4ee5\u5982\u300c\u65b9\u6cd5\u300d\u4e2d\u6240\u8ff0\u4e4bELISA\u5f97\u77e5TGF-β1\u4e4b\u6d53\u5ea6\u3002(B<\/strong>) \u7a33\u5b9a\u8868\u73b0luciferase\u4e4bMMTV\/PyVmT <\/em>\u7ec6\u80de\uff0c\u7531\u5c3e\u90e8\u9759\u8109\u6ce8\u5165\u672a\u4ea4\u914d\u4e4bFVB\u6bcd\u9f20\u3002\u5728\u63a5\u53d7\u7ec6\u80de\u6ce8\u5c041\u5c0f\u65f6\u4e4b\u524d\uff0c\u8001\u9f20\u5728\u56fe\u4e2d\u6240\u6807\u90e8\u5206\u4e4b\u80f8\u90e8\uff0c\u4ee510 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\n\t\u502a  \u5e08  \u8bc4  \u8bba<\/strong><\/h4>\n

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<\/section>\n

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<\/section>\n

\n\t\u6c49\u5510\u4e2d\u533b \u502a\u6d77\u53a6  <\/strong><\/p>\n

\n\t\u8c28\u8bb0\u4e8e\u4f5b\u5dde2009\u5e7403\u670822\u65e5  <\/strong> <\/strong><\/p>\n<\/section>\n","protected":false},"excerpt":{"rendered":"

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