中药三七抑制二乙基亚硝胺诱发大鼠肝癌血管生成的研究

Effect of Prescription of Sanchi on Rats with Hepatocarcinoma Induced by Diethylnitrosamine

目的研究中药三七抑制二乙基亚硝胺(DEN)诱发大鼠肝癌血管生成的作用。方法 82只Wistar雄性大鼠,根据随机数字表法分为中药组、西药组、联合组、模型组,每组18只;空白组10只,以100 ppm DEN饮水法诱发大鼠肝癌模型。中药组用三七水煎剂灌胃,西药组静脉注射贝伐单抗,联合组给予三七灌胃、贝伐单抗静脉注射,模型组和空白组均给予等量的生理盐水灌胃。分别于12周末和18周末分批处死大鼠,分析中药组、西药组、联合组、模型组和空白组大鼠肝标本,检测大鼠肝细胞癌血管内皮生长因子(VEGF)、血管生成素-1(Ang-1)、血管生成素-2(Ang-2)、血管生成素-2受体(Tie-2)、缺氧诱导因子-1α(Hif-1α)表达水平及肝癌组织微血管密度(MVD)。结果 12周末及18周末时Ang-1 mRNA在中药组、西药组、联合组较模型组肝癌组织中表达均上调,而Ang-2、Tie-2、HIF-1α及VEGF mRNA表达均下调(P<0.05)。联合组、西药组、中药组的MVD也均较模型组明显减少(P<0.05)。结论三七在HCC肿瘤血管生成和进展中可能通过抑制Ang-2、Tie-2 HIF-1α及VEGF而发挥预防作用。

Objective To study the effect of prescription of Sanchi on rats with hepatocarcinoma induced by diethylnitrosamine （ DEN） .Methods Eighty-two male Wistar rats were divided into Chinese medicine group ,western medicine group,combination group,model group and blank group according to the data table method .The hepatocarci-noma rats were induced by DEN （100 ppm）.The Chinese medicine group was given water decoction of Sanchi by lav-age,the western medicine group was given bevacizumab with intravenous injection ,the combination group was given water decoction of Sanchi by lavage and bevacizumab with intravenous injection ,the model group and blank group were given the same amount of saline by lavage .The rats were killed at the end of the 12th week and 18th week,respective-ly,and the liver specimens of rats were analyzed among Chinese traditional medicine group ,western medicine group , combination group ,model group and blank group .The expression levels of detected vascular endothelial growth factor （VEGF）,Ang-1,Ang-2,Tie-2,HIF-1αof rat with hepatocellular carcinoma and the microvessel density （MVD） of hepatocarcinoma tissues were detected .Results At the end of the 12th week and 18th week,Ang-1 mRNA expres-sion in hepatocellular carcinoma （ HCC） tissues obviously up-regulated in Chinese medicine group ,western medicine group and combination groups compared with model group ,while Ang-2,Tie-2,HIF-1αand VEGF mRNA expression declined compared with model group（P〈0.05）.The MVD of combination group,western medicine group and Chinese medicine group declined significantly （ P〈0 .05 ） .Conclusion Sanchi might play a preventive role in the HCC tumor angiogenesis and progress by inhibiting Ang-2,Tie-2,HIF-1αand VEGF.