| Aims:This study aims to explore the effects of spironolactone on epithelial-mesenchymal transition in rats with diabetic nephropathy.Methods:Wistar rats were administered intraperitoneal injection of STZ (60mg/kg) for the preparation of a diabetic model. After 4 weeks, rats with urinary protein> 30mg/d were deemed to be a successful model of diabetic nephropathy, and were randomly divided into a diabetic nephropathy (DN group), a spironolactone group (SP group) and a normal group (N group). The SP Group was treated with 50mg/(kg. d) spironolactone. After 4 weeks, rats were sacrificed to collect urine, blood plasma, and kidney tissue for detection of 24h urinary protein, creatinine and renal pathological changes respectively. Radioimmunoassay was used to detect aldosterone concentration in plasma and kidney tissue whilst E-cadherin ET1 and a-SMA protein expression were determined by immunohisto- chemistry and Western Blot Detection. RT-PCR was used to detect E-cadherin, ET1 and a-SMA mRNA expression.Results:Compared with the normal group, creatinine, urinary protein excretion and aldosterone levels in renal tissue of the diabetic nephropathy rats were significantly higher. E-cadherin protein and mRNA expression was significantly reduced, whilst a-SMA protein and mRNA expression was raised. Urinary protein excretion and serum creatinine were reduced. E-cadherin protein and mRNA upregulation withα-SMA protein and mRNA expression were lower in diabetic nephropathy rats treated with spironolactone than in diabetic nephropathy rats. Renal ET-1 protein and mRNA synthesis demonstrated marked increases in the spironolactone treatment group.Conclusion:Local aldosterone in kidney tissue is involved in epithelial-mesenchymal transition and up-regulates the expression of ET1 in rats with diabetic nephropathy. Spironolactone can block the role of aldosterone in epithelial-mesenchymal transition, demonstrating a renoprotective effect, and abolish changes in ET1. |
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