舒肝颗粒对酒精性肝纤维化的疗效及其机制的实验研究

Shugan granule's efficacy and its mechanisms in prevention and treatment of experimental alcoholic liver fibrosis in rats

[目的]探讨舒肝颗粒对酒精性肝纤维化的防治作用及其机制。[方法]用乙醇灌胃的方法制备酒精性肝纤维化大鼠模型。雌性Wistar大鼠随机分为正常对照组、酒精组和舒肝颗粒干预组。实验24周末观察生化和病理改变。[结果]酒精组血清白细胞介素6、肿瘤坏死因子α水平与干预组比较差异有统计学意义(P<0.01)。酒精组Masson胶原染色纤维化较重,而干预组无明显纤维化。24周末,酒精组肝组织中丙二醛与正常组、干预组比较,明显升高(P<0.01);酒精组及干预组肝组织中超氧化物歧化酶活性,明显高于正常组(P<0.05)。SABC免疫组化染色显示24周酒精组肝窦周围及汇管区结蛋白染色阳性物质明显增多,而正常组和干预组仅在汇管区周围有少量阳性物质。[结论]舒肝颗粒具有良好防治大鼠酒精性肝纤维化的作用,其作用机制可能与降低脂质过氧化、抑制肝星状细胞激活转化有关。

[Objective] To investigate the efficacy of Shugan granule in the treatment of ethanol-induced liver fibrosis in the rats and its mechanisms by observing the changes of biochemistry and pathology. [Methods] Female Wistar rats were randomly divided into 3 groups： normal group, ethanol-fed group , interventional group . The rats of the interventional group were administered with Shugan granule 0.5 g/kg twice daily. Forty per cent （vol / vol） ethanol 8 g/kg· d was given to the rats of the ethanol-fed groups and the interventional groups by intragastric infusion once in the morning. The animals were decollated at the 24th weekend. Blood samples were used for testing： IL-6 and TNF-α. Rat livers were harvested to examine the pathological changes by Masson＇s trichrome （MT） staining. Hepatic stellate cells （HSC） were determined by immunohistochemical SABC stain. The concentrations of SOD and malonaldehyde （MDA） of the livers were measured by biochemical analysis. [Results] With MT staining, fibrosis was developed in the ethanol-fed group at the 24 th weekend. But in the interventional group, there was no obvious fibrosis at the same time. Hepatic MDA contents were increased in the ethanol-fed groups at the 24 th weekend, and there was significant difference between the ethanol-fed and interventional groups （P〈0.05）. The contents of SOD were increased by ethanol. Desmin＋ cells were found around portal vein and perisinus in the alcohol group in 24 th week. Whereas, this kind of cell was found only near portal vein in the interventional group and the normal group, and much less than that of the ethanol-fed group. [Conclusion] Shugan granule has beneficial effects in prophylaxis and the treatment of alcoholic liver diseases in rats. The mechanisms may be contributed to reducing lipid peroxidation and inhibiting HSC initiation.