罗格列酮通过下调糖尿病大鼠肾血管生成素-2表达发挥肾保护作用  

The Renal Protection o Rosiglitasone in Diabetic Rats Through Downregulation of Angiopoietin-2

作　　者：顾红卫[1,2] 倪兆慧 顾乐怡[1] 严玉澄[1] 戴慧莉[1] 李宁丽[3] 张敏芳[1] 牟姗[1] 钱家麒[1] 

机构地区：[1]上海交通大学医学院附属仁济医院肾脏科,上海200127 [2]上海同济大学医学院附属东方医院 [3]上海交通大学医学院上海免疫研究所,上海200127

出　　处：《中国中西医结合肾病杂志》2013年第8期670-673,I0001,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金："973"项目(No.2012CB517602);上海市科委基础重点项目(No.10JC1410100);上海市卫生局科研基金资助项目(No.2010L063A)

摘　　要：目的:探讨血管生成素(angiopoietins,Ang)及其受体Tie-2和血管内皮生长因子(VEGF)在糖尿病大鼠肾组织中的表达以及罗格列酮对其表达的影响。方法:18只SD大鼠随机分为正常对照组(C组)、糖尿病组(D组)和糖尿病罗格列酮治疗组(R组)。实时定量RT-PCR和免疫组化方法分别检测3组大鼠肾组织中Ang-1、Ang-2、Tie-2和VEGF的表达;Western印迹法检测3组大鼠肾组织中Ang-2的蛋白表达。结果:实时定量RT-PCR和与Western印迹法结果显示,Ang-2糖尿病组[(80.88±28.30)&(0.76±0.19)]表达,较对照组[(47.81±20.50)&(0.28±0.07)]明显升高(P<0.05);经罗格列酮治疗后,Ang-2表达[(52.35±8.50)&(0.45±0.04)]显著下调(P<0.05)。相关分析显示,Ang-2mRNA水平与尿蛋白/肌酐值(Upro/Ucr)、平均肾小球体积(VG)和肾小球细胞外基质相对含量(RM)呈显著正相关(r=0.505,P=0.027;r=0.490,P=0.033;r=0.471,P=0.042)。结论:Ang-2的异常表达可能在早期糖尿病肾病的发病机制中起了重要的作用。罗格列酮可能通过下调糖尿病大鼠肾组织Ang-2的表达而发挥肾保护作用。Objective： To study the expression of angiopoietins （Ang） , Tie - 2 and vascular endothelial growth factor （VEGF） in the renal tissue of diabetic rats and the effect of peroxisome proliferators activated receptor-γ （PPARγ,）activator, Rosigli tazone on their expression. Methods ：SD rats were randomized into normal control group （group C）, diabetes group （group D）and dia betes treated with Rosiglitazone（ group R）. Renal expression of VEGF, Ang - 1, Ang - 2 and their receptor Tie - 2, were assessed using real - time reverse transcription - polymerase chain reaction and immunohistochemistry, while the protein expression of Ang - 2 was detected by Western Blot. Results： Result Compared with the group C, the expression of Ang -2 was significantly increased in the group D （ P 〈 0.05 ）. Compared with the group D, the expression of Ang - 2 was significantly decreased in the group R（P 〈 0.05 ）. Ang - 2 mRNA expression correlated positively with Urine Protein/Urine Creatinine, mean glomerular volume and glomerular relative extra cellular matrix value （ r = 0. 505, P = 0. 027 ; r = 0. 490, P = 0. 033 ; r = 0.471, P = 0.042）. Conclusion： Ang - 2 may play an important role in the development of diabetic nephrepathy. Rosiglitazone might exert a protection on diabetic renal injury,possibly partly through the down regulation of Ang -2 expression in the renal tissue.

关 键 词：糖尿病肾病 血管生成素 血管内皮生长因子 罗格列酮 

分 类 号：R587.1[医药卫生—内分泌]