盐酸吡格列酮对糖尿病大鼠尿nephrin排泄的影响

Effect of different dosages of pioglitazone on the excretion of urinary nephrin in STZ-induced diabetic rats

目的观察不同剂量盐酸吡格列酮(PIO)对糖尿病大鼠尿nephrin(UNE)排泄的动态影响,探讨噻唑烷二酮类药物(TZDs)对肾小球足细胞的保护作用。方法 32只链脲佐菌素(STZ)诱导的糖尿病大鼠随机分为4组:模型组(DM组)和不同剂量PIO干预组[DR1、DR2、DR3组,分别给予PIO:10、20、30 mg/(kg.d)],设正常对照组(NC组)。干预前后动态监测血糖(BG)、糖化血红蛋白(HbA1c)、尿白蛋白(UACR)、UNE、尿肌酐(Ucr)。结果①4组糖尿病大鼠BG及HbA1c均明显高于NC组(P<0.01),而4组之间差异无显著性。②4周末,DR2和DR3组UACR较DM组显著降低(P<0.01),而DR1组与DM组间差异无显著性;8周末,各干预组UACR均较模型组明显降低(P<0.01),DR2组和DR3组UACR较DR1组降低明显(P<0.05)。③0周5组大鼠尿中均检测到nephrin,但差异无显著性;4周末DM组UNE排泄显著高于各干预组(P<0.05),但各干预组间差异无显著性;8周末各干预组UNE较DM组均显著降低(P<0.05),DR2和DR3组UNE与DR1组相比均显著降低(P<0.05),而DR2与DR3组间UNE差异无显著性。④Pearson相关分析显示UNE与UACR存在正相关(r=0.881,P<0.01)。结论 PIO可降低糖尿病大鼠UNE的排泄,且具有一定的剂量依赖性。

Objective To observe the effect of different dosages of hydrochloride pioglitazone（PIO） on the excretion of urinary sediment nephrin（UNE） in STZ-induced diabetic rats,and to investigate the protective effects of thiazolidinediones（TZDs） on podocyte.Methods 32 STZ-induced diabetic rats were randomly divided into following four groups： model diabetic rats（DM group）,10,20 and 30 mg/（kg·d）PIO-treated diabetic rats（DR1,DR2 and DR3 group,respectively,n=8）,in addition,8 healthy rats were served as normal control group（NC group）.The peripheral blood glucose（BG）,glycated haemoglobin（HbA1c）,urinary albumin（UACR）,UNE and urinary creatinine were measured in the experimental period.Results ① The BG and HbA1c levels in all diabetic rats were significantly increased（P0.01,versus group NC）,but no significant differences among diabetic rats.② At the 4th week,UACR was significantly decreased in DR2 and DR3 group（P0.01,versus group DM）,which in DR1 group decreased slightly;At the 8th week,UACR in PIO-treated group was significantly lower than that of DM group,which in DR2 and DR3 group were significantly lower than that of DR1 group.③ At the first day,UNE could be detected in five groups,but no significant differences;At the 4th week,UNE was significantly reduced in PIO-treated groups（P0.05,versus DM group）,but no differences among the PIO-treated groups;At the 8th week,UNE was significantly reduced in PIO-treated groups（P0.05,versus DM group）.UNE was significantly decreased in DR2 and DR3 group（P0.05,versus DR1 group）,but no difference between DR2 and DR3 group.④ Pearson correlation analysis showed that UNE was positively correlated with UACR（r=0.881,P0.01）.Conclusion PIO can restrain UNE with a dose-dependent mode.