四逆散加味对肝纤维化大鼠肝组织中TGF-β1 及其受体基因和蛋白表达的影响

Effect of SiniSan Jiawei on TGF-β1 and its Receptor Gene and Protein Expression in Liver Tissue of Rats with Hepatic Fibrosis

摘要:

目的: 探讨四逆散加味治疗肝纤维化的疗效及其作用机制。方法: 将80 只 Wister 大鼠随机分为正常组,模型组,四逆散组(4.0 g·kg^-1),四逆散加味高、中、低剂量组(依次为14,7,3.5 g·kg^-1),四逆散加味预防组(7 g·kg^-1),秋水仙碱组(0.2 mg·kg^-1),除正常组外,其余各组均采用猪血清 ip 诱发肝纤维化每周2次,每次0.5 mL/只,连续10周。采用反转录-聚合酶反应(RT-PCR)和链霉菌抗生物素蛋白-过氧化物酶连结法(S-P)检测肝组织转化生长因子β₁ (TGF-β₁)及其受体基因和蛋白表达。结果: 与正常组比较,模型组大鼠肝组织中TGF-β₁及其受体基因和蛋白大量表达(P<0.01);经四逆散加味治疗后与模型组比较,大鼠肝组织中TGF-β₁及其受体基因和蛋白表达量显著下调(P<0.01);与秋水仙碱组比较,四逆散加味中剂量组、四逆散加味预防组TGF-β₁及其受体基因和蛋白表达下调更为显著(P<0.01)。结论: 四逆散加味治疗肝纤维化的可能作用机制是通过减少肝组织中TGF-β₁的产生及下调转化生长因子受体(TGFR)表达而减少肝星状细胞活化,减少肝组织中细胞外基质(ECM)的生成,而起到抗肝纤维化和保护肝细胞损伤的作用。

Abstract:

Objective: To discuss the curative effect and action mechanism of Sinisan Jiawei flavored in treatment of hepatic fibrosis. Method: Eighty Wister rats were randomly divided into eight groups:normal group;model group;Sinisan group(4.0 g·kg^-1);high dose group, mediate dose group and low dose group (14,7,3.5 g·kg^-1) and prevention group(7 g·kg^-1) of supplemental Sinisan;colchicine group(0.2 mg·kg^-1). Except the norrmal groups,all the other groups were given pig serum to induce liver fibrosis twice a week, 0.5 mL/per rat for 10 weeks. By RT-PCR and immunohistochemical S-P method were used to monitor liver tissue transforming growth factor β₁(TGF-β₁) and its receptor gene and protein expression. Result: After treatment of Sinisan Jiawei flavored the rats liver tissue TGF beta 1 and its receptor gene and protein expression significantly lower (P<0.01)compared with the model group compared.Compared with colchicine group, the TGF-β₁ and its receptor gene and protein expression lowered more significantly (P<0.01). Conclusion: The action mechanism of Sinisan Jiawei flavored in treatment of hepatic fibrosis may reduce liver tissue TGF-β₁ and TGFR expression.