Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production

被引:175
作者
Prabhakar, Sharma
Starnes, Joel
Shi, Shuping
Lonis, Betty
Tran, Ruc
机构
[1] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA
[2] Texas Tech Univ, Hlth Sci Ctr, Dept Physiol, Lubbock, TX 79430 USA
[3] Texas Tech Univ, Hlth Sci Ctr, Dept Pathol, Lubbock, TX 79430 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2007年 / 18卷 / 11期
关键词
D O I
10.1681/ASN.2006080895
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The pathogenesis of diabetic nephropathy remains far from clear, partly due to the lack of a suitable animal model that mimics human renal disease in type 2 diabetes. In this study, the natural history of renal manifestations in ZSF(1) rats, a recently developed rodent model of type 2 diabetes, is described. Male ZSF(1) rats developed obesity and hyperglycemia by 20 weeks of age on a high-carbohydrate diet. They also developed systolic and diastolic hypertension, hypercholesterolemia, profound hypertriglyceridemia, proteinuria, and renal failure. Renal histology demonstrated changes consistent with early diabetic nephropathy, including arteriolar thickening, tubular dilation and atrophy, glomerular basement membrane thickening, and mesangial expansion. Furthermore, renal nitric oxide production was decreased, and homogenates from renal cortices demonstrated reduced expression of renal endothelial and inducible nitric oxide synthases. These changes were associated with increased urinary levels and renal expression of 8-hydroxydeoxyguanosine, an indicator of mitochondrial oxidative stress, as well as with increased renal peroxynitrite formation. Administration of either insulin or the antioxidant alpha-lipoic acid decreased proteinuria and oxidative stress, but only the former slowed progression of renal failure. We conclude that ZSF(1) rats represent the best available rat model to study nephropathy from type 2 diabetes and that the renal lesions are associated with increased oxidative stress and decreased renal nitric oxide availability.
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收藏
页码:2945 / 2952
页数:8
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