Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: The role of reducing oxidative stress in its protective property
Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: The role of reducing oxidative stress in its protective property
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DOI：
10.1016/j.diabres.2008.10.007
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发表时间：
2009-02-01
影响因子：
5.1
通讯作者：
Chung, Choon Hee
中科院分区：
文献类型：
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作者：
Nam, Soo Min;Lee, Mi Young;Chung, Choon Hee
糖尿病肾病是糖尿病最严重的并发症。氧化应激通过烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶和血管内皮生长因子（VEGF）途径在糖尿病肾病的发生发展中起重要作用。本研究采用2型糖尿病大鼠模型，观察了NADPH氧化酶抑制剂夹竹桃苷对糖尿病肾病的影响。将16只大冢长埃文斯德岛肥胖（OLETF）大鼠和9只长埃文斯德岛大冢（LETO）大鼠分为3组：LETO组（n = 9）、对照组（n = 7）和夹竹桃素治疗组（n = 9）。我们检查了体重、血糖水平、尿白蛋白-肌酐比值（ACR）和蛋白-肌酐比值（PCR）。术后50周处死大鼠，取肾脏行HE染色、VEGF免疫组化染色及VEGF mRNA实时荧光定量RT-PCR检测。为了检查氧化应激，我们检查了24小时尿8-OHdG（8-羟基-2 '-脱氧鸟苷）和MDA（丙二醛）。尿蛋白和白蛋白排泄减少后，夹竹桃麻素治疗，虽然夹竹桃麻素不能显着降低血糖水平。夹竹桃素治疗的OLETF大鼠肾小球和系膜扩张有改善。夹竹桃麻素能显著降低肾小球VEGF免疫组化染色的光密度值，降低24 h尿8-OHdG和MDA的浓度。从这些结果，这表明，夹竹桃素可能有潜力，以防止糖尿病肾病通过改善氧化应激。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n = 9), control OLETF rats (n = 7) and apocynin-treated OLETF rats (n = 9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24 h urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24 h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress. (C) 2008 Elsevier Ireland Ltd. All rights reserved.