去甲斑蝥素微球介入治疗大鼠肝癌疗效及其机制研究

目的探讨去甲斑蝥素-海藻酸/聚酸酐微球(norcantharidin-alginicacid/polyacidanhydridemicro-spheres,N-MS)介入治疗大鼠肝癌的作用及其机制。方法采用乳化-化学交联法制备N-MS。建立大鼠肝癌模型,将荷瘤大鼠随机分为空白对照组、去甲斑蝥素(norcantharidin,NCTD)组、空白微球(blankmicro-sphere,B-MS)组、NCTD-碘油组和N-MS组。各组荷瘤大鼠分别经肝动脉注入生理盐水、NCTD、B-MS、NCTD-碘油和N-MS。治疗后,观察各组大鼠生存时间、肝肿瘤体积和肝肿瘤坏死程度;采用TUNEL法检测各组大鼠肝肿瘤细胞凋亡指数;采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接法(streptavidin-biotinperoxidasemethod,SP)检测各组大鼠肝肿瘤细胞Ki-67的表达。结果治疗后,N-MS组大鼠的生存期较其他各组明显延长;肝肿瘤体积小于其他各组;肿瘤生长率和肝肿瘤细胞Ki-67的表达明显低于其他各组;肿瘤坏死程度和肝肿瘤细胞凋亡指数均高于其他各组,差异均有统计学意义。结论N-MS经肝动脉介入对大鼠肝癌具有较好的治疗作用,其作用机制与栓塞肿瘤微血管、缓慢释放NCTD、诱导肿瘤细胞凋亡和下调Ki-67的表达,从而抑制肿瘤细胞增殖有关。

Effects of interventional therapy with norcantharidin microsphere on hepatoma in rats and its mechanism

Objective: To investigate the effects of interventional therapy with norcantharidin-alginic acid/poly acid anhydride microspheres (N-MS) infusion via hepatic artery on hepatoma in rats. Methods: N-MS was prepared by emulsion-chemical crosslink technique. Eighty-nine hepatoma-bearing rats were randomly divided into five groups, which were normal saline group, norcantharidin (NCTD) group, blank microsphere (B-MS) group, NCTD-lipiodol group and N-MS group. Normal saline, NCTD, B-MS, NCTD-lipiodol and N-MS were injected via hepatic artery accordingly. After the interventional therapy, eight rats from each group were observed for survival time, and the rest rats were killed on the 8th day after intervention to measure the tumor volume and necrostic degree. The apoptotic index of liver tumor cells was detected by TUNEL staining, and the expression of ki-67 was assayed by immuno-histochemical streptavidin-biotin peroxidase method. Results: The survival time of the rats in the N-MS group was prolonged as compared with those in the other four groups, and the tumor volume of the rats in the N-MS group was smaller than those in the other four groups. The tumor growth rate and the expression level of ki-67 in the N-MS group were both significantly lower than those in the other four groups. The tumor necrotic degree and the apoptotic index in the N-MS group were significantly higher than those in the other four groups. Conclusion: Interventional therapy with N-MS could yield preferable therapeutic effects on hepatomas in rats. This anti-tumor efficacy may be associated with microvessel embolization in liver tumor and the sustained releasing of NCTD. Its inhibiting effect on tumor cell proliferation maybe result from decreasing the expression of Ki-67 and inducing the tumou cell apoptosis.