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目的:用大鼠Walker-256移植性肝癌模型研究ilexgenin A抗肿瘤作用以及对肿瘤血管内皮生长因子(VEGF)和微血管密度(MVD)的影响,以探讨ilexgenin A抗肝癌作用机制。方法:32只大鼠移植性肝癌模型随机分为4组:ilexgenin A高、低剂量(100,500 mg.kg-1.d-1)组,5-Fu(5 mg.kg-1,隔日1次)组,模型组。于造模成功后第8天ilexgenin A治疗组及5-Fu组ip给药,模型组分别ig生理盐水10 mL.kg-1给药,连续用药14 d后停药24 h,取血处死大鼠,取出瘤块称重,常规瘤体组织形态学观察,分离血清检测肝功能指标天冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT),用免疫组化法检测瘤块中VEGF和MVD的表达情况;另设正常组饲养大鼠8只,不进行造模及给药,供实验结束时作空白对照用。结果:ilexgenin A给药组瘤重明显低于模型组(P<0.01);ilexgenin A给药组及5-Fu血管条数目密集程度较模型组比较明显减少,ilexgenin A对血清AST,ALT活性升高有明显的拮抗作用,AST的含量与模型组比较差异显著(P<0.01);实验造模各组VEGF及MVD的表达水平均明显高于正常组(P<0.01);两者的表达均以模型组最高。结论:ilexgenin A可显著抑制大鼠体内癌细胞生长,对移植性肝癌所造成的肝功能损伤具有明显的保护作用,其作用机制可能与下调VEGF和MVD的表达水平有关。
OBJECTIVE: To study the anti-tumor effect of ilexgenin A and its effect on tumor vascular endothelial growth factor (VEGF) and microvessel density (MVD) in a rat model of Walker-256 liver transplantation to investigate the mechanism of anti-hepatoma effect of ilexgenin A. Methods: Twenty-two rat models of hepatocellular carcinoma were randomly divided into 4 groups: ilexgenin A high and low dose (100, 500 mg.kg-1.d-1), 5-Fu ) Group, model group. On the 8th day after successful model establishment, ilexgenin A treatment group and 5-Fu group were administered with ip, and the model group were given ig saline 10 mL.kg-1, discontinued after 14 days of continuous administration, The tumors were removed and weighed. The tumor histomorphology was observed. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were detected by ELISA. The VEGF and MVD expression; the other set the normal group of 8 rats fed, not modeling and administration for the end of the experiment for blank control. Results: The tumor weight of ilexgenin A group was significantly lower than that of the model group (P <0.01). The density of ilexgenin A group and 5-Fu vascular bundle was significantly decreased compared with the model group. The activity of ilexgenin A on serum AST and ALT activity (P <0.01). The expression levels of VEGF and MVD in each group were significantly higher than those in normal group (P <0.01). The expression of both of them was significantly higher than that of normal group The highest model group. CONCLUSION: ilexgenin A can significantly inhibit the growth of cancer cells in vivo and has a significant protective effect on liver injury induced by transplanted hepatocellular carcinoma. The mechanism may be related to the down-regulation of the expression of VEGF and MVD.