大黄水浸液对肝内胆汁淤积性肝损伤大鼠水道通蛋白8表达的影响

The effect of rhubarb aqueous extract on expression of aquaporin 8 in rats with intrahepatic cholestasis induced liver injury

目的观察大黄水浸液对急性肝内胆汁淤积性肝损伤大鼠肝脏水通道蛋白8(AQP8)表达的影响,探讨其可能的作用机制.方法采用4%ANIT 100 mg/kg 1次建立急性肝内胆汁淤积模型,在造模前48 h开始分别以6.0g/(kg·d)和3.0g/(kg·d)的大黄水浸液灌服干预,连续4 d;所有大鼠于灌服ANIT后48 h空腹麻醉下腹腔静脉取血,分离血清,检测血清AST、ALT、TBIL水平,酶联免疫检测血清胰高糖素水平;荧光定量PCR法检测肝组织AQP8mRNA表达;免疫组化法检测肝组织AQP8蛋白表达.结果模型组大鼠血清ALT、AST和TBIL水平比正常组增高(P<0.01),血清胰高糖素水平及肝组织AQP8mRNA和蛋白表达比正常组下降;应用大黄水浸液干预后,血清ALT、AST和TBIL水平比模型组降低(P<0.05),血清胰高糖素水平及肝组织AQP8mRNA和蛋白表达比模型组增加(P<0.05).结论大黄水浸液能改善急性肝内胆汁淤积造成的肝损伤,其机制可能是通过促进胰高糖素分泌、增加肝脏组织AQP8mRNA与蛋白表达水平实现的.

Objective To observe the effect of rhubarb aqueous extract on the expression of aquaporin 8(AQP8)in rats with acute intrahepatic cholestatic liver injury and explore its possible mechanism.Methods The acute intrahepatic cholestasis model was established with 4%ANIT 100 mg/kg once,and the intervention was administered with 6.0 g/(kg·d)and 3.0 g/(kg·d)rhubarb aqueous infusion at 48 hours before modeling for 4 consecutive days.All rats were taken from the abdominal vena cava under fasting anesthesia 48 h after the administration of ANIT,the serum was separated,and the serum AST,ALT,TBIL levels were detected by biochemical methods,the serum glucagon levels were detected by enzyme-linked immunosorbent assay;the liver tssue AQP8mRNA was detected by fluorescence quantitative PCR Expression;immunohistochemical method to detect AQP8 protein expression in liver tsse.Results The levels of serum ALt,AST and TBIL in the model group were signifcantly higher than those in the normal group(P<0.01),and the levels of serum glucagon and the expression of AQP8mRNA and protein in liver tsse were significantly lower than those in the normal group.After intervention with rhubarb aqueous infusion,serum ALT The levels of AST and TBIL were significantly lower than those in the model group(P<0.05),and the levels of serum glucagon and the expression of AQP8mRNA and protein in liver tsse were significantly higher than those in the model group(P<0.05).Conclusion Rhubarb aqueous extract can improve liver injury caused by acute intrahepatic cholestasis.The mechanism may be achieved by promoting the secretion of glucagon and increasing the expression of AQP8mR NA and protein in liver tssue.