祛湿化瘀方治疗小鼠实验性非酒精性脂肪性肝炎合并肝纤维化的疗效

Efficacy evaluation of the Qushi Huayu Formula for the treatment of experimental non-alcoholic steatohepatitis with hepatic fibrosis in mice

目的:明确祛湿化瘀方对实验性非酒精性脂肪性肝炎(NASH)合并肝纤维化的疗效。方法:运用高反式脂肪酸高糖饮食诱导29周构建小鼠NASH合并肝纤维化模型,并予祛湿化瘀方灌胃给药4周,设奥贝胆酸为阳性对照药。观察各组小鼠血清丙氨酸氨基转移酶(ALT)及天门冬氨酸氨基转移酶(AST)活性、空腹血糖(FBG)、胰岛素(INS)和胰岛素抵抗指数(HOMA-IR)水平,肝组织甘油三酯(TG)与羟脯胺酸(HYP)含量,肝组织病理,肝纤维化相关指标:肝组织Ⅰ型胶原蛋白(Col-Ⅰ)、α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β(TGF-β)的mRNA及蛋白的表达。结果:祛湿化瘀方可显著降低NASH肝纤维化小鼠血清ALT、AST活性及FBG、INS和HOMA-IR(P<0.01,P<0.05),降低肝组织TG及HYP含量(P<0.05,P<0.01);显著改善肝组织脂肪变性、炎症及气球样变、降低纤维化分期,显著降低肝组织Col-Ⅰ、α-SMA和TGF-β的mRNA及蛋白表达(P<0.05,P<0.01)。结论:祛湿化瘀方可改善实验性NASH肝纤维化,为其治疗NASH肝纤维化的临床应用及药物研发提供依据。

Objective:To assess the therapeutic effect of a Qushi Huayu Formula(QSHY)on experimental non-alcoholic steatohepatitis(NASH)combined with liver fibrosis.Methods:A mouse model of NASH combined with liver fibrosis was induced by high trans-fatty acid and high sugar diet for 29 weeks.The mice were treated with QSHY by gavage for the last 4 weeks,and obeticholic acid was used as a positive control.The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity;fasting blood glucose(FBG),insulin(INS),and homeostatic model assessment for insulin resistance(HOMA-IR);triglyceride(TG)and hydroxyproline(HYP)content in liver tissue;the histopathological changes in liver tissues and related indicators of liver fibrosis were observed in each group of mice,such as the mRNA and protein expression of type I collagen(Col-Ⅰ),alpha-smooth muscle actin(α-SMA)and transforming growth factor-beta(TGF-β)were measured.Results:QSHY could significantly reduce serum ALT and AST activities,FBG,INS and HOMA-IR(P<0.01,P<0.05)and the contents of TG and HYP(P<0.05,P<0.01),improve the liver tissue pathology of mice,including steatosis,lobular inflammation,and ballooning.The mRNA and protein levels of Col-Ⅰ,α-SMA and TGF-βin liver tissue were significantly lower than those in the model group(P<0.05,P<0.01).Conclusion:Qushi Huayu Formula can improve liver fibrosis in experimental NASH,which provides a basis for its clinical application and drug development in the treatment of NASH complicated with liver fibrosis.