摘要
目的:通过"方-效-证"相结合研究,明确茵陈蒿汤对二甲基亚硝胺(di methylnitrosamine,DMN)或四氯化碳(carbon tetrachloride,CCl4)两种造模方式所致的肝硬化模型大鼠的疗效特点。方法:分别采用DMN和CCl4建立大鼠肝硬化模型,以肝纤维化已经形成并向肝硬化发展的时期(CCl4造模8周后)及其肝硬化成型后(DMN造模4周后)作为干预治疗的切入点,横向比较茵陈蒿汤在不同模型中的药效。基因芯片技术检测肝脏基因表达情况。结果:在DMN模型中,随着造模时间的延长,模型大鼠血清丙氨酸氨基转移酶(alanineaminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、γ谷氨酰转移酶(gamma-glutamyl transferase,GGT)活性和总胆红素(total bilirubin,TBil)含量逐渐升高,均于4周时达到高峰(P<0.01);血清白蛋白(albumin,ALB)含量逐渐降低,4周时降至最低(P<0.01);与6周模型对照组比较,茵陈蒿汤组大鼠血清ALT、AST和GGT活性及TBil含量显著降低(P<0.05或P<0.01),血清ALB含量显著升高(P<0.05)。在CCl4模型中,茵陈蒿汤显著降低血清ALT、AST和GGT活性(P<0.05),但对血清TBil和ALB含量的改善没有显著作用。茵陈蒿汤能显著改善DMN大鼠肝脏病理改变,降低羟脯氨酸含量,但对CCl4模型则没有显著作用。基因芯片结果表明,在CCl4模型中,茵陈蒿汤显著抑制Fas、Bax和caspase-3的表达,促进Bcl-xL的表达,但不能抑制CCl4诱导的肝细胞凋亡,反而促使酪氨酸激酶受体上调了4.8倍。结论:茵陈蒿汤对DMN和CCl4两种大鼠肝硬化模型都表现出了疗效,但对DMN模型的干预尤其是降低肝组织羟脯氨酸含量、改善肝组织病理变化及调控凋亡基因等的作用显著优于CCl4模型。
Objective：To investigate the different efficacy of Yinchenhao Decoction（YCHD）,a compound traditional Chinese herbal medicine,for liver cirrhosis induced by dimethylnitrosamine（DMN） or carbon tetrachloride（CCl4） in rats.Methods：To induce liver fibrosis,0.5% DMN solution（2 mL/kg body weight,i.p.） was given three consecutive days a week to male Wistar rats for 4 weeks.Cirrhotic rats were randomly divided into DMN group,YCHD group,Xiaochaihu decoction group by the end of the fourth week to accomplish a 2-week recipe treatment course.In CCl4-induced liver fibrosis model,50% CCl4-olive solution was injected subcutaneously to rats at a dose of 2 mL/kg body weight twice a week to duplicate rat cirrhosis model.After 8 weeks,rats were divided into CCl4 group,CCl4 plus YCHD group and Xiaochaihu decoction group.For the YCHD group,YCHD was administered intragastrically once a day for 4 weeks.For DMN or CCl4 model,by the end of 6 or 12 weeks respectively,rats were sacrificed for sampling to detect liver function,hepatic histological changes,hydroxyproline（Hyp） content and apoptosis-related gene expressions.Results：In DMN liver fibrosis model,hepatic fibrosis was obvious at week 2 and cirrhosis was evident at week 4 in DMN-treated rats.Compared to 6-week DMN group,hepatic pathological changes and liver function were improved significantly and content of Hyp decreased remarkably in YCHD group.In CCl4-induced liver fibrosis model,hepatic fibrosis was obvious at 8 weeks and cirrhosis was evident at 12 weeks in CCl4-treated rats.Compared to 12-week CCl4 group,hepatic pathological changes and liver function were not obviously improvement in YCHD group.The results of gene chip showed that YCHD significantly decreased Fas,Bax and caspase-3 gene expressions,and increased Bcl-xL gene expression in the liver of DMN model.However,in the model induced by CCl4,YCHD did not inhibit hepatocyte apoptosis induced by CCl4,but increased tyrosine kinase receptor gene expression by 4.8 times.Conclusion：YCHD exerts more s
出处
《中西医结合学报》
CAS
2011年第4期423-434,共12页
Journal of Chinese Integrative Medicine
基金
国家自然科学基金资助项目(No.90409020
No.30701070
No.81001486)
上海市科学技术委员会启明星计划(No.08QA14062)
中国博士后基金(No.20090450726)
上海市重点学科建设项目(No.Y0302)
上海市教育委员会E-研究院建设计划项目(No.E03008)
上海高校创新团队建设项目
上海市中医临床重点实验室资助项目
关键词
中草药
肝硬化
二甲基亚硝胺
四氯化碳
方证相应
大鼠
drugs
Chinese herbal
liver cirrhosis
dimethylnitrosamine
carbon tetrachloride
recipe-oriented syndrome
rats
