吡格列酮对糖尿病大鼠尿足细胞排泄及肾小球WT-1分布的影响  

Effect of Pioglitazone on the Excretion of Urinary Podocytes and Distribution of WT-1 in Glomerulus in Diabetic Rats

作　　者：邹敏书[1] 余健[1] 聂国明 刘雪梅[1] 

机构地区：[1]广州军区武汉总医院儿科,湖北武汉430070

出　　处：《医学临床研究》2008年第9期1641-1643,1646,共4页Journal of Clinical Research

摘　　要：【目的】探讨吡格列酮对糖尿病(DM)大鼠尿白蛋白及足细胞排泄及肾小球足细胞特异性标志蛋白Wilm's tumor-1(WT-1)分布的影响。【方法】24只SD大鼠分为3组,正常对照组;DM组(链脲佐菌素65mg/kg腹腔注射诱导DM大鼠模型);吡格列酮组(DM大鼠给予吡格列酮20mg/kg.d灌胃)。检测各组第10周的尿白蛋白排泄率(UAER)、甘油三酯(TG)及血糖(BG)。间接免疫荧光法检测尿沉渣WT-1阳性即为尿液足细胞(UPC)。观察肾小球细胞数及细胞外基质(ECM)聚积;免疫荧光染色检测肾小球WT-1的分布。【结果】DM组UPC、UAER、TG、BG均较对照组明显升高(P<0.01)。吡格列酮组TG、BG较对照组明显升高(P<0.01),UPC亦升高(P<0.05)。与DM组相比,吡格列酮组UPC、UAER、BG显著降低(P<0.01),TG亦降低(P<0.05)。病理组织肾小球荧光染色示WT-1在对照组正常,DM组呈节段性明显缺失,吡格列酮组缺失较轻。DM组肾小球细胞数及ECM/肾小球毛细血管襻面积较吡格列酮组增多(P<0.05或P<0.01))。UPC与UAER呈正相关(rs=0.46,P<0.05),而与TG无显著相关性(rs=0.37,P>0.05)。【结论】尿液中脱落足细胞检测可作为判断DM病情活动性的标志之一。吡格列酮可减轻DM大鼠UAER及UPC的排泄,抑制肾小球细胞数及ECM增殖,恢复肾组织WT-1表达而有肾保护作用。[Objective]To investigate the effect of pioglitazone on urinary albumin excretion rate（UAER）. urinary podocytes（UPC）and the distribution of Wilm＇s tumor-1 （WT-1） in glomerulus in diabetic rats. [Methods] Twenty four Sprague-Dawley rats were divided into three groups： normal control group, diabetes mellitus group Einduced with 65mg/kg streptozotocin（STZ） in peritoneal injection, DM group2, pioglitazone treatment group（treated with 20mg/kg. d pioglitazone by intragastric administration）. UAER, triglyceride （TG）and blood glucose（BG）were measured after 10 weeks of pioglitazone treatment. Podocyte-specific marker protein-WT-1 was detected in urinary sediment by indirect immunofluorescene and urinary WTl-positive cells were identified as UPC. The distribution of WT-1 in glomerulus, glomerular cellularity and extracellular matrix（ECM） were observed. [Results] UPC, UAER,TG and BG in DM group were significantly higher than those in control group（ P 〈0.01）. TG and BG in pioglitazone treatment group were significantly higher than those in control group（ P 〈0.01）, and UPC also increased（ P 〈0.05）. UPC, UAER and.BG in pioglitazone treatment group were significantly lower than those in group DM（ P 〈0. 01）. but TG was not statistical .difference（ P 〈0.05）. The expression of WT 1 was normal in glomeruli in control group, focally absent in DM group, and not obviously absent in pioglitazone treatment group. Compared with pioglitazone treatment group, glomerular cellularity and the area ratio of ECM to glomerular capillary were significantly increased in DM group（ P 〈0.05 or P〈0.01）. The level of UPC had positive correlation with UAER（rs =0.46, P 〈0. 05） and no correlation with TG（rs = 0. 37, P 〉0.05）. [Conclusion] Urinary podocyte can be one of the markers to predict the development of DM. Pioglitazone could contribute to the decrease of UAER and UPC excretion, and inhibit glomerular cellularity and ECM proliferation, and restore the expression o

关 键 词：糖尿病 实验性 疾病模型 动物 肾小球 大鼠 

分 类 号：R587.1[医药卫生—内分泌]