吡格列酮对糖尿病大鼠肾组织TSP1表达的影响

目的 探讨噻唑烷二酮类(thiazolidinediones,TZD)药物吡格列酮对1型糖尿病(diabetes mellitus,DM)大鼠肾组织中血小板反应蛋白-1(thrombospondin-1,TSP1)及转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达的影响.方法 40只Sprague-Dawley(SD)大鼠随机分为正常对照组(NC)、模型组(DM,链脲佐菌素单次腹腔注射)、吡格列酮治疗组(DP)、给药对照组(NP).干预后10周末,检测各组24 h尿蛋白定量、血肌酐(serum creatinine,Scr)及肾脏肥大指数;RT-PCR法观察肾组织TSP1和TGF-β1 mRNA表达水平;免疫组化法观察肾组织内TSP1和TGF-β1蛋白表达水平.结果 DP组与DM组比较,血糖水平差异无统计学意义(P>0.05),但24 h尿蛋白和肾脏肥大指数明显降低(P<0.05).与Nc和NP组相比,DM及DP组TSPl和TGF-β1表达显著增高(P<0.01);与DM组相比,DP组TSP1和TGF-β1表达明显降低(P<0.05).结论 吡格列酮对DM大鼠具有直接肾脏保护作用,其机制不依赖于胰岛增敏(降糖),可能与降低肾组织TSP1和TGF-β1表达有关.

The Effect of Pioglitazone on the Expression of Thrombospondin-1 in the Kidney of Diabetic Rats

Objective To investigate the effect of pioglitazone on the expression of thrombospondin-1(TSP1)and transfor ming growth factor-β1 (TGF-131)in the kidney of diabetic rats.Methods Forty Sprague-Dawley(SD)rats were randomly divided into 4 groups:normal control(NC),streptozocin-induced diabetic mellitus(DM),diabetic rats treated with pioglitazone(DP)and normal control rats treated with pioglitazone(NP).24-h urine protein quantity,serum creatinine(Scr) and kidney hypertrophy index were measured after treatment for 10 weeks,and the expression of TSP1 and TGF-β1 in the kidney was detected by using RT-PCR and immuohistochemistry.Results As compared with DM group,urine protein level and kidney hypertrophy index were significantly attenuated in DP group(P<0.05),but there was no significant difference in plasma glucose between them(P>0.05).As compared with NC and NP groups,the expression of TSP1 and TGF-β1 was significantly elevated in the kidney of DM and DP groups(P<0.01).Both TSP1 and TGF-β1 expression in DP group was lower than in DM group(P<0.05).Conclusion Pioglitazone can exert a direct protective effect on the kidney in diabetic rats,which is independent of the role of insulin sensitizer,and the mechanism may be associated with the decreased TSP1 expression in the kidney.