二甲双胍对糖尿病大鼠肝脏中重要转运蛋白表达的影响

目的：研究二甲双胍对糖尿病大鼠肝脏中重要转运蛋白表达的影响.方法：利用高脂肪饲料与链脲佐菌素（STZ）诱导产生糖尿病模型大鼠.将造模后大鼠分为模型对照组、二甲双胍低剂量组（30 mg·kg^-1·d^-1）、二甲双胍高剂量组（100 mg·kg^-1·d^-1）,口服给药4周,同时设正常对照组.检测并比较不同组别大鼠肝脏组织中P糖蛋白（P-gp）与多药耐药相关蛋白（MRP）2蛋白表达量与相应mRNA表达水平.结果：二甲双胍高、低剂量组的P-gp与MRP2蛋白表达及mRNA水平均明显低于模型对照组（P＜0.05）,且二甲双胍高剂量组明显低于二甲双胍低剂量组（P＜0.05）.结论：二甲双胍可能通过抑制肝脏的P-gP与MRP2蛋白表达及mRNA水平,从而发挥降糖作用,可能是其作用机制之一.

Effect of Metformin on Drug Transporter Expression in Liver of Diabetic Rats

Objective：To study the effect of metformin on the drug transporter expression in liver of diabetic rats.Methods：High-fat diet and streptozocin （STZ）injection were applied to induce diabetes in rats.The diabetic rats and the normal rats were divided into nonetreatment group,metformin low-dose group and mefformin high-dose group.After the four-week treatment,the rat livers were harvested and the P-gp/MRP2 protein expression level and mRNA expression level were evaluated.Results：The important liver drug transporters （P-gp and MRP2） protein expression and mRNA expression level showed reduced expression level after the long term metformin treatment in diabetic model rats（P 〈 0.05） when compared to the model group.The high-dose treatment was more effective than the low-dose （P 〈0.05）.Conclusion：Metformin may decrease sugar by depressing the expression of protein between P-gp and MRP2 and the level of mRNA in hepar,which is possible one of the mechanism of it.