血管生成抑制素抑制胃癌浸润转移的实验研究  

The Inhibition by Angiostatin on the Growth and Metastasis of Gastric Cancer in the Nude Mice

作　　者：陈雪华[1] 刘炳亚[1] 卢卫新[2] 郭礼和[2] 朱丽华[2] 朱正纲[1] 林言箴[1] 

机构地区：[1]上海第二医科大学附属瑞金医院外科上海消化外科研究所,200025 [2]中国科学院上海细胞生物学研究所,200031

出　　处：《胃肠病学》1999年第2期83-85,共3页Chinese Journal of Gastroenterology

摘　　要：目的：实验研究血管生成抑制素抑制胃癌浸润转移的作用。方法：以Ｓｅｐｈａｒｏｓｅ亲和层析柱从血浆成分中分离出纤溶酶原，再用弹性蛋白酶酶切，经Ｓｅｐｈａｒｏｓｅ ４Ｂ－Ｌｙｓｉｎｅ亲和层析柱分离出血管生成抑制素。以完整组织块裸鼠胃壁内原位种植建立胃癌转移模型，于肿瘤种植当天，给实验动物２４μｇ（１．２ｍｇ／ｋｇ）血管生成抑制素作腹腔内注射，以后每天给以１２μｇ（０．６ｍｇ／ｋｇ）以相同剂量的纤溶酶原行腹腔内注射作为对照，相同体积的生理盐水腹腔内注射作为空白对照，治疗共进行３周，肿瘤种植后１０周处死动物，测量肿瘤体积，观察转移情况，并用免疫组化法检测肿瘤微血管密度。结果：从血浆成分中分离出的纤溶酶原分子量为９４ｋＤ，经弹性蛋白酶酶切后分离所得血管生成抑制素有４１～４３ｋＤ和５１～５３ｋＤ两种片段。动物实验表明，血管生成抑制素对胃癌生长及转移有一定的抑制作用，具体为：肿瘤生长抑制了５４．０％，腹膜转移抑制了５５．６％，肝转移抑制了６１．９％；纤溶酶原对胃癌生长及浸润转移均无作用。结论：血管生成抑制素可从血浆成分中分离出。血管生成抑制素对胃癌生长及转移具有一定的抑制作用。Background/Aims: To study experimentally the inhibition by angiostatin on gastric cancer angiogenesis and metastasis. Methods: Plasminogen was isolated from human plasma by Sepharose chromatography, angiostatin was isolated by first by elastase cutting and then by Sepharose 4B-Lysine chromatography isolation. Nude mice model of metastatic gastric cancer was set up by implanting intact tumor tissue orthotopically. On the day of operation, 24μg(1.2mg/kg) of angiostatin was administered intraperitoneally followed by a daily dose of 12μg (0.6mg/kg) for three weeks. In the control groups, similar dosage of plasminogen or similar volume of NS were given intraperitoneally. Ten weeks after implantation, all the mice were sacrificed and autopsied. Microvasular density was measured by inununohistochemistry. Results:The molecular eight of plasminogen isolated from the plasma was 94kD. The catalyzation of plasminogen by elastase gave rise to two fragments of 41-43kD and 51-53kD. Growth of the implanted tumor was significantly reduced in size in the mice treated with angiostatin (inhibition rate, 54.0%). Tumor metastasis to the liver and peritoneum was also significantly inhibited by angiostatin (inhibition rate, 61.9% and 55.6% respectively). The micro vascular density was also decreased significantly in the treatment group. Conclusions: Angiostatin could be produced from human plasma. Angiostatin exhibited an inhibitory effect both on tumor growth and tumor metastasis.

关 键 词：血管生成抑制素 胃癌 纤溶酶原 腹腔内注射 癌生长 转移 肿瘤种植 酶切 亲和层析 实验动物 

分 类 号：R735.2[医药卫生—肿瘤] R730[医药卫生—临床医学]