吡格列酮对糖尿病大鼠肾组织TSP1表达的影响  

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

作　　者：付玲[1] 代甜[1] 刘建社[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院肾内科,武汉430022

出　　处：《华中科技大学学报（医学版）》2009年第6期725-728,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省科技攻关计划资助项目(No.2005AA301C33)

摘　　要：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(serumcreatinine,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TSP1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。Objective To investigate the effect of pioglitazone on the expression of thrombospondin-1（TSP1）and transforming growth factor-β1（TGF-β1）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多-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.

关 键 词：糖尿病肾病 吡格列酮 血小板反应蛋白-1 转化生长因子-Β1 

分 类 号：R587.24[医药卫生—内分泌]