复方鳖甲软肝片抑制大鼠酒精性肝纤维化的实验研究

Experimental research on Fufangbiejiaruangan inhibiting alcoholic hepatic fibrosis in rats

目的探讨复方鳖甲软肝片对实验性大鼠酒精性肝纤维化的抑制作用机制。方法40只Wistar雄性大鼠随机分为正常组、模型组、中药组和西药组。模型组、中药组、西药组以"酒精-吡唑-玉米油"混合液灌胃并饲以高脂饮食,正常组每天用生理盐水灌胃,并以普通饲料喂养。16周后中药(复方鳖甲软肝片)组和西药(复方牛胎肝提取物片)组开始药物治疗。给药4周后检测血生化、肝组织病理学变化、肝组织中TGF-β1蛋白表达变化。结果酒精性肝纤维化模型大鼠肝功能显著异常,肝纤维化明显。经4周治疗,与模型组比较,中药组及西药组血清中ALT、AST、HA含量显著下降(P<0.01)。光镜观察结果显示,中药组和西药组大鼠肝血窦周围胶原明显减少,相邻血窦间的纤维联络基本消失。免疫组化染色结果显示,中药组大鼠肝组织中TGF-β1蛋白含量显著下降。结论复方鳖甲软肝片通过下调TGF-β1表达抑制胶原纤维的产生,阻止纤维化的发展,从而有效阻止和逆转酒精性肝纤维化的进程。

Objective To explore the inhibiting effect of Fufangbiejiarnangan on alcoholic hepatic fibrosis in rats. Methods Forty Wister male rats were randomly divided into 4 groups, the control group, the model group, traditional Chinese medicine （ TCM ） treatment group and western medicine treatment group. The model group, TCM treatment group and western medicine treatment group were administered with intragastrical perfusion of ＂alcohol-pyrazole-corn oil＂ mixture and given high-fat diet for 16 weeks to prepare rat models of alcoholic hepatic fibrosis while the control group was given saline. Then TCM treatment group was treated with Fufangbiejiaruangan and western medicine treatment group with compound embryonic bovine liver extract tablets. After 4 weeks of treatment, hepatic fibrosis indices, liver tissue pathology and expression of transforming growth factor- β 1 （TGF-β1） in liver tissues were detected. Results Rat models of alcoholic hepatic fibrosis showed abnormal hepatic function and obvious hepatic fibrosis. After 4 weeks of treatment, compared with the model group, alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and hyaluronic acid （HA） decreased significantly （P〈0.01） in the serum in the two treatment groups. It was shown by light microscopy that collagen content around hepatic sinusoids decreased obviously, and there was almost no fiber connection among blood sinusoids in rat livers of the two treatment groups. Immunohistochemistry showed that expression of TGF- β 1 decreased significantly in TCM treatment group. Conclusion Fufangbiejiaruangan can inhibit the generation of collagen fibers and prevent the progression of hepatic fibrosis by down-regulating the expression of TGF-β 1. Therefore, Fufangbiejiaruangan can inhibit and reverse the progression of alcoholic hepatic fibrosis in rats effectively.