Sun Ming-yu, Wang Lei, Mu Yong-ping, Liu Cheng, Bian Yan-qin, Wang Xiao-ning, Liu Ping
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Zhong Xi Yi Jie He Xue Bao. 2011 Apr;9(4):423-34. doi: 10.3736/jcim20110412.
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 (CCl(4)) in rats.
To induce liver fibrosis, 0.5% DMN solution (2mL/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 CCl(4)-induced liver fibrosis model, 50% CCl(4)-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 CCl(4) group, CCl(4) plus YCHD group and Xiaochaihu decoction group. For the YCHD group, YCHD was administered intragastrically once a day for 4 weeks. For DMN or CCl(4) 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.
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 CCl(4)-induced liver fibrosis model, hepatic fibrosis was obvious at 8 weeks and cirrhosis was evident at 12 weeks in CCl(4)-treated rats. Compared to 12-week CCl(4) 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 CCl(4), YCHD did not inhibit hepatocyte apoptosis induced by CCl(4), but increased tyrosine kinase receptor gene expression by 4.8 times.
YCHD exerts more significant therapeutic effects on DMN-induced than CCl(4)-induced cirrhosis in rats in Hyp content and pathological change in liver tissue.
探讨复方中药茵陈蒿汤(YCHD)对二甲基亚硝胺(DMN)或四氯化碳(CCl₄)诱导的大鼠肝硬化的不同疗效。
为诱导肝纤维化,每周连续3天给雄性Wistar大鼠腹腔注射0.5% DMN溶液(2 mL/kg体重),共4周。在第4周结束时,将肝硬化大鼠随机分为DMN组、YCHD组、小柴胡汤组,进行为期2周的方剂治疗。在CCl₄诱导的肝纤维化模型中,每周2次给大鼠皮下注射50% CCl₄ -橄榄油溶液,剂量为2 mL/kg体重,以复制大鼠肝硬化模型。8周后,将大鼠分为CCl₄组、CCl₄加YCHD组和小柴胡汤组。YCHD组每天灌胃给药1次,共4周。对于DMN或CCl₄模型,分别在第6周或第12周结束时处死大鼠取样,检测肝功能、肝脏组织学变化、羟脯氨酸(Hyp)含量及凋亡相关基因表达。
在DMN肝纤维化模型中,DMN处理的大鼠在第2周肝纤维化明显,第4周肝硬化明显。与6周的DMN组相比,YCHD组肝脏病理变化和肝功能显著改善,Hyp含量显著降低。在CCl₄诱导的肝纤维化模型中,CCl₄处理的大鼠在第8周肝纤维化明显,第12周肝硬化明显。与12周的CCl₄组相比,YCHD组肝脏病理变化和肝功能无明显改善。基因芯片结果显示,YCHD显著降低DMN模型肝脏中Fas、Bax和caspase - 3基因表达,增加Bcl - xL基因表达。然而,在CCl₄诱导的模型中,YCHD并未抑制CCl₄诱导的肝细胞凋亡,但使酪氨酸激酶受体基因表达增加4.8倍。
YCHD对大鼠DMN诱导的肝硬化在Hyp含量和肝组织病理变化方面的治疗效果比CCl₄诱导的肝硬化更显著。