吡格列酮对糖尿病大鼠肾脏的保护作用及其机制探讨

目的观察吡格列酮对糖尿病大鼠肾脏的保护作用并探讨其机制。方法采用链脲佐菌素(STZ)诱导糖尿病模型。24只大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)、吡格列酮干预组(3mg·kg-1·d-1,DT组),每组8只。12周末,测定各组相关生化指标。运用比色法检测肾皮质中丙二醛(MDA)的含量、铜锌超氧化物歧化酶(Cu-ZnSOD)及过氧化氢酶(CAT)的活性。同时留取肾标本作电镜观察。结果与NC组相比,DM组和DT组血糖、胆固醇、甘油三酯、血清胰岛素、C肽、尿素氮、血肌酐、肾重/体重和24h尿蛋白定量差异有统计学意义。DM组与NC组比较,肾皮质Cu-ZnSOD、CAT活性明显降低(P<0.01),MDA含量明显增加(P<0.01)。DT组与DM组比较,血糖、胆固醇、甘油三酯、血清胰岛素、C肽、尿素氮、血肌酐差异无统计学意义(P>0.05),肾重/体重和24h尿蛋白定量明显降低(P<0.05);肾皮质CAT和Cu-ZnSOD活性增加(P<0.05),肾皮质MDA含量降低(P<0.05)。结论吡格列酮对糖尿病大鼠肾脏有保护作用且此作用不依赖其降糖、降脂机制,可能与吡格列酮的抗氧化机制有关。

Renoprotective effects of pioglitazone in diabetic rats

Objective To investigate the renoprotective effects of pioglitazone and mechanism underlying these effects in diabetic rats. Methods Murine diabetic models were induced with streptozotocin (STZ). We randomized 24 rats into three groups (n=8 for each), namely, the normal control group (NC group), diabetic group (DM group), and the pioglitazone-treated diabetic group (3mg·kg-1·d-1, DT group). After 12 weeks, a set of biochemical data, including serum glucose, total cholesterol (TC), triglyceride (TG), blood insulin, blood C-peptide, blood urea nitrogen (BUN), serum creatinine (Scr), ratio of kidney weight to body weight (KW/ BW), and 24-hour urinary protein were measured in each group. The activities of antioxidant enzymes in renal cortex, including Cu-Zn superoxide dismutase (Cu-Zn SOD), catalase (CAT), and malondialdehyde (MDA) were measured by chromatometry. In addition, the renal tissue was observed under light microscope and electron microscope. Results Compared with NC group, significant changes were noted in the levels of serum glucose, TC, TG, blood insulin, blood C-peptide, BUN, Scr, KW/BW and 24-hour urinary protein both in DM group and DT group. The activities of Cu-Zn SOD and CAT were much lower (P<0.01), while the level of MDA was much higher (P<0.01) in DM group than in NC group. There were no marked differences in the levels of serum glucose, TC, TG, blood insulin, blood C-peptide, BUN and Scr between DT group and DM group (P>0.05). However, compared with DM group, the KW/ BW and 24-hour urinary protein in DT group showed obvious decrease (P<0.05), the activities of Cu-Zn SOD and CAT increased significantly, and the level of MDA was lowered (P<0.05). Conclusion Pioglitazone demonstrated renoprotective effects against early-stage diabetic nephropathy, probably through antioxidative mechanisms, which is independent of its actions on glucose and blood lipids.