血管抑素对仓鼠胰腺癌肝脏转移瘤抑制作用的实验研究

ANTITUMOR EFFECT OF ANGIOSTATIN ON LIVER METASTASIS OF PANCREATIC CANCER IN SYRIAN GOLDEN HAMSTER MODEL

目的 研究血管抑素 (angiostatin)对仓鼠胰腺癌肝脏转移瘤生长的影响。方法 建立仓鼠胰腺癌肝脏转移瘤模型后 ,治疗组 (15只 )注射纯化的人血管抑素。对照组 (15只 )以相同的方式注射盐水。移植 2 1天后处死。测量肝脏转移灶的数量和最大直径 ,检测肝肾功及体重的变化。转移瘤标本免疫组化染色 ,微血管密度计数 ,Ag NOR计数 ,计算凋亡指数 (AI)。数据进行统计学处理。结果 治疗组肝脏表面的转移灶均数及最大直径以及转移瘤标本微血管密度及凋亡指数均显著小于对照组。治疗组和对照组的 Ag- NOR计数差异不明显。两组仓鼠的体重和肝肾功血液生化检查治疗前后没有显著变化。结论 血管抑素通过抑制血管生成 ,诱导仓鼠胰腺癌肝脏转移瘤的细胞凋亡 。

Objective To Study on the antitumor effect of angiostatin on liver metastasis of pancreatic cancer in Syrian golden hamster model.Methods After building the liver metastatic models of pancreatic cancer, the purified human angiostatin was injected into the hamsters’spleen on treatment group (n=15) .The hamsters on control group (n=15) were received saline injections . All hamsters were sacrificed at 21 days after implantation, and then the liver specimen of each hamster were removed and the number and the largest diameter of liver surface metastases were measured. Liver and kidney function and body weights of both groups were measured. The liver specimens were processed for hematoxylin and eosin staining and immunohistochemistry, and then the average microvessel density (MVD) was quantified. The Ag-NOR score was used to evaluate the tumor proliferation. The apoptotic index was also evaluated.Result The number and the largest diameter of liver surface metastases of treatment group were much smaller than that of control group; the difference of MVD and apoptotic index between the treatment and control group was significant,but the difference of Ag-NOR score between them can not be found. There was no body weight loss in both groups when they were sacrificed, and there was no significant difference in liver and kidney function (AST, ALT, LDH, BUN, CREA).Conclusion Angiostatin potently inhibits the growth of liver metastasis of pancreatic cancer by specifically inhibiting endotherial proliferation and increasing the number of tumor cell apoptosis.