二甲双胍对糖尿病大鼠肝脏中重要转运蛋白表达的影响  

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

作　　者：程志英[1] 李霞[1] 张淑珍[1] 刘芳莉[1] 王莉[2] 

机构地区：[1]武警总医院药剂科,北京100039 [2]武警总医院检验科,北京100039

出　　处：《中国药师》2014年第6期901-903,共3页China Pharmacist

摘　　要：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Pgp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。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.

关 键 词：二甲双胍 糖尿病 转运体 P-糖蛋白 MRP2 

分 类 号：R965.1[医药卫生—药理学]