中药栓塞微球的临床前药效学研究

Preclinical Pharmacodynamic Study of Traditional Chinese Medical Embolization Microsphere

目的考察中药动脉栓塞微球的肝肿瘤动脉栓塞、细胞凋亡、坏死,肝功能变化,免疫及增敏作用。方法在透视下经连接管缓慢注入白兔肝肿瘤供血动脉,采用原位缺口末端标记法检测细胞的凋亡指数,免疫组织化学法检测肿瘤细胞中Bax和Bcl-2蛋白的表达,考察肿瘤细胞凋亡率、坏死率,肝功能变化及氯喹增敏作用;以小鼠碳粒廓清法研究免疫调节作用。结果中药栓塞微球中、高剂量组肿瘤生长抑制率与空白A组相比有显著差异(P<0.01);细胞凋亡指数低、中剂量组与A组相比有显著差异(P<0.01),与不含氯喹B组相比,差异显著(P<0.05);与低、中、高剂量组相比动物的ALT和AST值均显著低于B组(P<0.05);中药栓塞剂高、中剂量组廓清指数K值明显升高,吞噬指数α值也有一定增高(P<0.05)。结论实验提示中药栓塞微球具有形成肝肿瘤动脉栓塞,诱导肝癌细胞凋亡、坏死,保肝,增敏效应及免疫调节作用。

Objective To study the hepatic artery embolization,cell apoptosis,tumor necrosis,liver function,immune and sensitization effect of traditional Chinese medical（ TCM） embolization microsphere. Methods Slowly inject the TCM embolization microsphere into the liver tumor blood supply arteries of rabbits in perspective of connecting pipe; use in situ and labeling method to detect cell apoptosis index; use immune histochemical method to detect tumor cells in the expression of Bax and Bcl- 2 protein; investigate cell apoptosis rate,tumor necrosis rate,liver function changes and chloroquine sensitization effects; use carbon clearance method to investigate immune modulating function in mice. Results Compared with the blank group A,the tumor growth inhibition rate of the medium and high does TCM microspheres group showed significant differences（ P〈0. 01）; the apoptosis index of low,medium dose group showed significant defference compared with group A（ P〈0. 01）,compared with chloroquine- free group B,the difference was significant（ P〈0. 05）,the ALT and AST values of animals in group B were significantly lower that those in low,medium and high dose groups（ P〈0. 05）; the expurgation index K of high and medium group raised significantly,the index of alpha value also raised（ P〈0. 05）. Conclusion TCM embolization microsphere is effective in forming liver tumor embolization,making necrosis and apoptosis of liver cancer cells,protecting liver,producing sensitization and immune modulating.