二甲双胍对2型糖尿病模型大鼠肾组织nephrin表达的影响

Effects of metformin on expression of renal tissue nephrin in type 2 diabetes mellitus rats

目的观察不同剂量二甲双胍(MET)对2型糖尿病(T2DM)模型大鼠肾组织nephrin表达的影响,了解其对肾小球足细胞的保护作用。方法高脂饲料喂养结合腹腔注射小剂量链脲佐菌素(STZ)建立T2DM大鼠模型,给予不同剂量[150、300、500 mg/(kg·d)]MET干预治疗(MET1组、MET2组、MET3组),并设立糖尿病模型组(T2DM组)和正常对照组(NC组)。8周后,观察各组大鼠血糖(BG)、糖化血红蛋白(HbA 1c)、尿素氮(BUN)、尿白蛋白和尿nephrin排泄的情况以及肾脏组织病理改变和nephrin表达的变化。结果8周末,MET三组BG、HbA 1c、尿白蛋白/尿肌酐(UACR)、基底膜厚度(GBMT)和足突融合率(FRFP)明显低于T2DM组,高于NC组(P<0.05);MET2、MET3组低于MET1组(P<0.05)。MET组血BUN、尿nephrin/尿肌酐(UNER)低于T2DM组(P<0.05),MET3与MET1组差异有统计学意义(P<0.05)。MET组肾组织nephrin蛋白和mRNA表达较T2DM组显著升高(P<0.05),但是低于NC组(P<0.05);各MET组间nephrin蛋白表达差异无统计学意义,MET3组nephrin mRNA表达高于MET1组(P<0.05)。结论 MET可减轻T2DM模型大鼠肾组织nephrin表达的减少和保护足细胞,并有一定的剂量依赖性。

Objective To observe the effects of different doses of metformin（MET） on the expression of renal tis- sue nephrin protein and mRNA in type 2 diabetes mellitus（T2DM） model rats and understand its protective effect on glomerular podocytes. Methods The model rats of T2DM were established by being fed with high fat-diet and intraperitoneal injection of low dose of streptozotocin （STZ）. Diabetic rats were divided into different dose metform- in groups （group MET1 ,group MET2 and group MET3, 150,300, 500 mg/（kg·d）, respectively）,T2DM model group （T2DM group） and normal control group （NC group） were also set up. After 8 weeks,blood glucose （BG） , glycated hemoglobin （ HbA1 c）, urinary albumin/urine creatinine （ UACR）, urinary nephrin excretion, renal tissue pathological changed and nephrin expression were detected. Results The levels of BG, HbA1 c, UACR, glomerular basement membrane thickness （GBMT） and food process fusion ratio （FRFP） in MET groups were significantly lower than those of T2DM group, while higher than those of NC group （ P 〈 0. 05 ）, and those above in MET2, MET3 were lower significantly compared with MET1 group（ P 〈0. 05 ） ; the levels of blood BUN and urinary neph- tin/urine creatinine （UNER） in MET groups were lower than those of T2DM group （P 〈 0.05 ）, there was statisti- cally significant difference between MET3 and MET1 group （ P 〈 0.05 ） ; the expression of renal tissue nephrin pro- tein and mRNA in MET groups were significantly increased compared with that of T2DM group （ P 〈 0. 05 ）, but lower than that of NC group （ P 〈 0. 05 ） ; the expression of nephrin protein had no statistically significant difference among MET groups, while the expression of nephrin mRNA in MET3 group was higher than that of MET1 group （P 〈0 . 05 ）. Conclusion MET can alleviate the down-regulation of renal tissue nephrin expression and provide some protection against glomerular podocyte damage in T2DM rats with a dose-dependent manner.