二甲双胍对2型糖尿病模型大鼠尿nephrin排泄的影响

Effects of metformin on urinary nephrin excretion in type 2 diabetes rats

目的 :观察二甲双胍对2型糖尿病模型大鼠尿nephrin(UNE)排泄的动态影响,探讨二甲双胍对糖尿病肾小球足细胞的保护作用。方法:将高脂膳食联合小剂量链脲佐菌素(streptozotocin,STZ)诱导的2型糖尿病大鼠随机分为3组:糖尿病模型组、二甲双胍干预组、优降糖干预组,并设正常对照组。干预前后监测血糖(BG)以及尿白蛋白(UALB)和尿nephrin排泄、8周末糖化血红蛋白(Hb A1c)的变化。结果:13组糖尿病大鼠BG及Hb A1c均明显高于正常组(P<0.05);经二甲双胍和优降糖干预后,4、8周末2组BG和Hb A1c均明显低于2型糖尿病模型组(P<0.05),但差异无统计学意义(P>0.05);24、8周末各糖尿病大鼠尿白蛋白/肌酐比(UACR)明显高于正常组(P<0.05);与2型糖尿病模型组比较,二甲双胍和优降糖组UACR值明显降低(P<0.05),4周末,两干预组间无显著性差异(P>0.05),8周末,两组间差异有统计学意义(P<0.05);30、2周末,4组大鼠尿nephrin/肌酐比(UNER)差异无统计学意义,4、8周末,各糖尿病大鼠UNER均明显高于正常组(P<0.05),二甲双胍和优降糖干预组UNER明显低于糖尿病模型组(P<0.05),且二甲双胍组低于优降糖组(P<0.05);4Pearson相关分析显示UNER与UACR存在正相关(r=0.846,P<0.05)。结论 :二甲双胍可以降低糖尿病肾病大鼠尿nephrin的排泄,提示对肾小球足细胞可能存在保护作用,该作用不完全依赖于血糖的降低。

Objective:To observe the effect of metformin on urinary nephrin excretion in type 2 diabetic model rats and investigate its protection of glomerular podocytes. Methods: Type 2 diabetes SD rats induced by high fat diet / streptozotocin(HFD-STZ) were randomly divided into 3 groups: the diabetic model group, the metformin group, the glibenclamide group,and the normal control group. Blood glucose(BG), urine albumin(UALB) and nephrin excretion were monitored before and after the intervention, and glycosylated hemoglobin(Hb A1c) was measured at the end of the study. Results:(1)BG and Hb A1 c levels of diabetic rats were significantly higher than those of normal group(P < 0.05); BG and Hb A1 c levels of the metformin and glyburide group were significantly lower than those of the type 2 diabetic model group(P < 0.05) at the end of the 4thand 8thweek, but there were no significant differences between the two intervention groups.(2)At the end of the 4thand 8thweek, UACR in all diabetic rats was significantly higher than that of the normal group(P < 0.05), which was significantly decreased in the metformin and glyburide group when compared with the type 2 diabetic model group(P < 0.05). There were no significant differences between the two intervention groups(P > 0.05) at the4 th week, but statistically differences were found at the 8thweeks(P < 0.05).(3)There were no significant differences of UNER among the 4 groups at the end of the 0th and 2nd weekend. At the end of the 4thand 8thweek, UNER in the diabetic groups was significantly higher than that of the normal group(P < 0.05). UNER was significantly decreased in the metformin and glyburide group compared with the diabetic model group. The level of UNER in the metformin group was obviously lower than that of the glyburide group(P < 0.05).(4)Pearson correlation analysis showed that UNER was positively correlated with UACR(r = 0.846, P < 0.05).Conclusion: Metformin can decrease the excretion of urinary nephrin and provide some protection for glomerular podocyte in diabeticrats, which is not completely dependent on its hypoglycemic effect.