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Aldose Reductase Inhibitor Ameliorates Renal Vascular Endothelial Growth Factor Expression in Streptozotocin-Induced Diabetic Rats

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Purpose: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. Materials and Methods: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg ˙ kg-1 ˙ day-1) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg ˙ kg-1 ˙ day-1)treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. Results: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 ± 11.12, 16.11 ± 9.95, and 84.85 ± 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. Conclusion: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.

Abstract

Purpose: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. Materials and Methods: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg ˙ kg-1 ˙ day-1) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg ˙ kg-1 ˙ day-1)treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. Results: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 ± 11.12, 16.11 ± 9.95, and 84.85 ± 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. Conclusion: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.

참고문헌 (32)

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