| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
In this study, we investigated the role of free radicals in the diabetic nephropathy. The superoxide anions are produced by NADPH oxidase. We revealed that. NADPH oxidase isoforms exist in the podocyte, glomerular endothelium, macula densa, distal convoluted tubule and fibroblast. In the hypertension model, SHR, NADPH oxidase expression in the kidney is enhanced contributing to the increase in tubuloglomerular feedback response. In the streptozotocin-induced diabetic rats, renal expression of NADPH oxidase is also enhanced and its products were increased in the urine and kidney associated with microalbuminuria. The enhanced radicals damage tubular endocytosis process of albumin via megalin in the proximal tubule, and this may contribute to microalbuminuria in the early stage of diabetic rats. As NADPH oxidase is regulated by angiotensin II, ACE inhibitor and AT1 receptor blocker (ARE) suppress the expression of NADPH oxidase and reduce radical production and microalbuminuria. The treatment with ACE inhibitor and ARE show a renoprotective effect via suppression of NADPH oxidase.
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