Effects of NADPH oxidase inhibitor in diabetic nephropathy
Effects of NADPH oxidase inhibitor in diabetic nephropathy
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DOI：
10.1111/j.1523-1755.2005.00287.x
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发表时间：
2005-05-01
影响因子：
19.6
通讯作者：
Wilcox, CS
中科院分区：
文献类型：
--
作者：
Asaba, K;Tojo, A;Wilcox, CS
背景我们使用夹竹桃素来验证烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶产生的超氧阴离子（O-2（-））是大鼠糖尿病肾病发生的基础这一假设。方法。在用链脲佐菌素诱导大鼠糖尿病（DM）后2 ~ 8周给予夹竹桃麻素（16 mg/kg/d）。DM增加过氧化氢（H2 O2）、脂质过氧化产物（LPO）、一氧化氮产物（NOx）和蛋白质的排泄。糖尿病大鼠肾脏p47 phox、gp 91 phox和内皮型一氧化氮合酶（eNOS）表达增加，系膜基质增加，纤维连接蛋白和I型胶原表达增加。夹竹桃麻素可抑制糖尿病大鼠肾脏H2 O2、LPO和蛋白质排泄的增加，增加肾脏NOx的生成，抑制肾脏gp 91 phox和p47 phox的表达，逆转系膜基质的扩张。尽管在糖尿病肾病模型中eNOS表达增强，但NADPH氧化酶的激活与p47 phox易位到膜是氧化应激和限制NO产生的基础。夹竹桃麻素可预防这些变化和相关的蛋白尿。
Background. We used apocynin to test the hypothesis that superoxide anion (O-2(-)) from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase underlies the development of diabetic nephropathy in the rat.Methods. Rats received apocynin (16 mg/kg/day) from 2 to 8 weeks after inducing diabetes mellitus (DM) with streptozotocin.Results. DM increased excretion of hydrogen peroxide (H2O2), lipid peroxidation products (LPO), nitric oxide products (NOx), and protein. The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), and increased mesangial matrix with expression of fibronectin and collagen I. Apocynin prevented the increase in excretion of H2O2, LPO, and protein in diabetic rats, increased renal NOx generation, and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox, and reverted the mesangial matrix expansion.Conclusion. Activation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO generation, despite enhanced eNOS expression in a model of diabetic nephropathy. Apocynin prevents these changes and the associated proteinuria.