消癥荣木散治疗大鼠肝硬化的实验研究

Effect of Xiaozheng Rongmu Powder for the Treatment of Liver Cirrhosis in Rats

目的探讨消癥荣木散对进展性CCl4大鼠肝硬化的治疗作用。方法采用50%CCl42mL/kg皮下注射(首次CCl4橄榄油溶液3mL/kg),每周2次,共8周(W),制备大鼠肝硬化模型;第9W开始模型大鼠随机分为模型对照组、消癥荣木散组及小柴胡汤组;用药的同时继续CCl4皮下注射至12W末。观察死亡率、腹水质量、肝功能、肝组织病理学、肝细胞增殖及肝纤维化相关指标mRNA表达变化。结果 8W模型大鼠血清ALT、AST、TBil显著升高(P<0.01),Alb显著下降(P<0.01),全部形成肝硬化并伴有腹水,肝组织α-SMA、TGF-β1、ColIA2、TNF-α、TIMP-1mRNA表达显著增加(P<0.01),MMP-13mRNA表达显著降低(P<0.01),并有少量肝细胞增殖;12W模型大鼠腹水质量、ALT、AST、TBil、α-SMA、TGF-β1、ColIA2、TNF-α、TIMP-1进一步升高,且腹水质量和TNF-α显著高于8W模型组,Alb及MMP-13进一步降低,肝细胞增殖明显受抑。与8W及12W模型组比较,消癥荣木散治疗后肝硬化程度明显减轻,ALT、AST、TBil、α-SMA、TGF-β1、ColIA2、TNF-α、TIMP-1均显著降低(P<0.01),Alb含量和MMP-13mRNA表达显著升高(P<0.05和P<0.01),肝细胞增殖活跃。结论具有消痰祛瘀补气功效的消癥荣木散能够逆转CCl4诱导的进展性肝硬化,该治疗方法可能为中医药逆转肝硬化带来新的希望。

Objective To observe the therapeutic effect of Xiaozheng Rongmu Powder（XRP）for the treatment of progressive CCl4-induced liver cirrhosis in rats.Methods Rat liver cirrhosis model was established by subcutaneous injection of 50% CCl4-olive oil 2 mL/kg twice a week for 12 weeks.Experimental rats were divided into the control group treated by saline and the two treatment groups,treated with XRP and Xiaochaihu Decoction,respectively,with the treatment starting from the 9th week of modeling.Rats were sacrificed at the terminal of experiment,the death rate,character of ascites,liver histological changes,liver function,mRNA expression of hepatocyte mitosis and the liver fibrosis associated markers in rats were observed.Results At the end of the 8th week of modeling,serum levels of ALT,AST and TBil were increased,and Alb decreased significantly in rats（P0.01）,cirrhosis formation with ascites could be seen in all rats.Meantime,levels of vascular smooth muscle α-actin,transforming growth factor-β1,collagen ⅠA2,tumor necrosis factor-α,tissue inhibistor of melalloproteinase-1 mRNA increased,while matrix melalloproteinase-13 mRNA were decreased significantly（P0.01）,with visible liver proliferation to some extents.Further changes of above-mentioned abnormalities and clear suppression of hepatocytes mitosis were found in the modeled rats at the end of the 12th week.As compared to those occurred in the control group,changes in the XRP treated group were significantly milder at the corresponding duration,and clearly active hepatocytes mitosis was shown.Conclusion XRP,a Chinese drug with the effect of dissolving phlegm,removing stasis and supplementing qi,could reverse the progress of cirrhosis formation induced by CCl4,and it brings potential new hope for the treatment of advanced cirrhosis by Chinese medicine.