Oxidative and Nitrosative Stress and Progression of Diabetic Nephropathy in Type 2 Diabetes
Oxidative and Nitrosative Stress and Progression of Diabetic Nephropathy in Type 2 Diabetes
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DOI：
10.1159/000297290
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Fukagawa, Masafumi
中科院分区：
文献类型：
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作者：
Fujii, Hideki;Kono, Keiji;Fukagawa, Masafumi
背景资料：一氧化氮（NO）在糖尿病肾病进展中的作用存在争议，其机制仍不清楚，特别是在非肥胖2型糖尿病中。为了研究非肥胖2型糖尿病肾病进展的机制，我们使用了自发性糖尿病Torii（SDT）大鼠，一种新建立的非肥胖2型糖尿病模型。研究方法：14只雄性SD大鼠作为对照组（20周龄，n = 6; 30周龄，n = 8），20周龄雄性SD大鼠分为2组：糖尿病组（DM，n = 8）和DM +胰岛素组（n = 8）。处死20周龄和36周龄大鼠，进行血、尿、组织形态学分析、内皮型一氧化氮合酶（eNOS）和NADPH氧化酶mRNA表达分析以及血压测量。结果：36周时，糖尿病组的NO代谢产物和8-羟基脱氧鸟苷（8-OHdG）显著高于其他两组。进一步的肾脏研究显示糖尿病组肾小球体积和系膜区增大，eNOS、8-OHdG和硝基酪氨酸免疫染色增强。氧化和亚硝化应激与肾小球体积和系膜面积增加呈正相关，胰岛素治疗后大部分恢复。结论：在SDT大鼠中，NO和氧化应激增加，表明这些在非肥胖2型糖尿病肾病进展中起关键作用。版权所有（C）2010 S. Karger AG，巴塞尔
Background: The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in nonobese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes. Methods: Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty-and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed. Results: At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed in creased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy. Conclusions: NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes. Copyright (C) 2010 S. Karger AG, Basel