芍药苷对胆汁淤积肝损伤保护作用机制研究

Mechanisms of paeoniflorin on cholestasis liver injury in mice

目的:研究芍药苷对胆汁淤积型肝损伤的保护作用机制。方法:将ICR小鼠随机分成正常对照组、模型对照组、芍药苷低、中、高剂量组。α-萘异硫氰酸酯(ANIT)诱导胆汁淤积型黄疸模型,观察各组药物对小鼠血清总胆红素(TBIL)、直接胆红素(DBIL)、胆汁酸(TBA)、丙氨酸转氨酶(ALT)和碱性磷酸酶(ALP)的影响,并用Western Blot检测小鼠肝组织中钠-牛磺胆酸盐共转运多肽(NTCP)和还原型辅酶Ⅱ氧化酶4(NOX4)蛋白的表达。结果:与正常对照组比较,模型对照组血清学指标均明显升高(P<0.01或P<0.05);肝组织中NOX4表达升高,而NTCP表达降低。与模型对照组比较,除芍药苷低剂量组ALT、TBIL,芍药苷中剂量组TBIL外,其余各剂量组ALT、ALP、TBIL、DBIL、TBA均明显降低(P<0.01)。芍药苷治疗组肝组织中NOX4表达较ANIT模型对照组表达减少,芍药苷给药组小鼠肝组织中的NTCP蛋白表达较ANIT组上升。结论:芍药苷具有一定的利胆退黄和保肝降酶作用,且该作用是通过抗氧化减轻肝细胞损伤和增强肝细胞对血液中胆盐的摄取的机制实现的。

Objective：To study the mechanisms of paeoniflorin on protecting cholestasis liver injury.Methods：The ICR mice were randomly divided into normal control group,model control group,paeoniflorin low,medium and high dose group.α-naphthalene isothiocyanate（ANIT） was used to make models of the mice cholestasis.Pharmacodynamic effect of paeoniflorin on model mice were evaluated by serum indices such as TBIL,DBIL,TBA,ALT and ALP,and the expression of NOX4 and NTCP in liver tissues were observed on the twelfth day.Results：Compared with normal control group,all serum indices of the model control group were significantly increased（P0.01 or P0.05）.The protein expression of NOX4 increased and the NTCP decreased in the model control group.Except the ALT,TBIL of the paeoniflorin low dose group and the TBIL of medium dose group,the serum indices of the remaining dose groups were significantly lower than those in model control group（P0.01）.Compared with the model control group,the protein of NOX4 decreased and the NTCP increased in the paeoniflorin groups.Conclusion：The paeoniflorin has the protective effect of liver and its mechanism might be related with its effect of anti-oxidation and increasing the bile salts uptake by hepatocytes.