大黄酚对慢性乙型病毒性肝炎大鼠肝功能损伤及肝脏纤维化作用及机制研究

Effect and mechanism of chrysophanol on liver function injury and liver fibrosis in chronic hepatitis B rats

目的探讨大黄酚对慢性乙型病毒性肝炎(CHB)大鼠肝功能损伤及肝脏纤维化的影响,并分析相关作用机制。方法60只雄性SD大鼠随机分为对照组、模型组及大黄酚低、高剂量(7.5、30 mg/kg)组和拉米夫定(10 mg/kg)组,每组12只。除对照组外,其余各组均尾iv乙型肝炎病毒(HBV)抗原构建CHB模型,造模成功后个给药组ip相应药物。采用全自动生化分析仪检测大鼠血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)水平;酶联免疫吸附(ELISA)法检测大鼠血清中透明质酸(HA)、层黏连蛋白(LN)、羟脯氨酸(HYP)水平;苏木精–伊红(HE)染色及Masson染色观察大鼠肝脏组织病理形态学及纤维化;Western blotting法检测大鼠肝脏组织中相关蛋白表达。结果与模型组比较,大黄酚7.5、30 mg/kg组和拉米夫定组大鼠血清中ALT、AST、TBIL、HA、LN、HYP水平均降低(P<0.05),大鼠肝组织病理性损伤和胶原纤维沉积显著改善,肝组织中α-平滑肌肌动蛋白(α-SMA)、I型胶原α1基因(COL1A1)、葡萄糖调节蛋白(GRP)78、GRP94及磷酸化真核生物翻译起始因子2α(p-eIF2α)/eIF2α、磷酸化蛋白激酶R样内质网激酶(p-PERK)/PERK均显著降低(P<0.05);且大黄酚30 mg/kg组、拉米夫定组大鼠血清和肝组织中上述指标均显著优于大黄酚7.5 mg/kg组(P<0.05)。结论大黄酚可能通过调控内质网应激减轻CHB大鼠肝功能损伤,改善大鼠肝纤维化。

Objective To investigate the effects of chrysophanol on liver function injury and liver fibrosis in rats with chronic viral hepatitis B(CHB),and to analyze the related mechanism.Methods Sixty male SD rats were randomly divided into control group,model group,chrysophanol low-dose and high-dose(7.5 and 30 mg/kg)groups,and lamivudine(10 mg/kg)group,with 12 rats in each group.Except for the control group,the CHB model was constructed by iv hepatitis B virus(HBV)antigen in the tail of the other groups,and the corresponding drugs were ip after successful modeling.The serum levels of AST,ALT,and TBIL were detected by automatic biochemical analyzer.The levels of HA,LN,and HYP in serum were detected by ELISA method.HE staining and Masson staining were used to observe the pathological morphology and fibrosis of liver tissue.The expression of related proteins in rat liver was detected by Western blotting.Results Compared with model group,the levels of ALT,AST,TBIL,HA,LN,and HYP in serum of rats in rheophanol 7.5,30 mg/kg groups and lamivudine groups were decreased(P<0.05),and pathological injury and collagen fiber deposition in liver tissue of rats were significantly improved.The levels ofα-SMA,COL1A1,GRP78,GRP94,p-EIF2α/EIF2α,p-PERK/PERK ratio in liver tissue were significantly decreased(P<0.05).The above indexes in serum and liver tissue of rats in chrysophanol 30 mg/kg group and lamivudine group were significantly better than those in chrysophanol 7.5 mg/kg group(P<0.05).Conclusion Chrysophanol may reduce liver function injury and improve liver fibrosis in rats with CHB by regulating endoplasmic reticulum stress.