Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats

摘要

Recent studies in animal models have revealed that mycophenolate mofetil (MMF) has certain protective effects against experimental diabetic nephropathy. The present study therefore aimed to investigate the hypothesis that diabetic nephropathy may be ameliorated by mycophenolate mofetil and benazepril treatment alone or in combination, and identify the potential underlying mechanisms in a rat model. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin. Rats were subsequently treated with benazepril, MMF or a combination of the two drugs, and blood glucose, normalized kidney weight, urine protein and serum creatinine were determined. The pathological changes in renal tissue were also observed. In addition, indices of epithelial mesenchymal transition, including a-smooth muscle actin (alpha-SMA) and transforming growth factor (TG-F)-beta 1 expression, were examined. Normalized kidney weight, urine protein and serum creatinine levels were significantly improved in the diabetic rats treated with benazepril or mycophenolate mofetil, compared with those of rats in the untreated diabetic group. Pathological changes in the kidney were detected concurrently with increasing kidney weight and urinary albumin excretion, with a similar trend in variation among groups. In addition, the expression of epithelial mesenchymal transition indices, including a-SMA and TGE-beta 1, in the renal tubule interstitium were significantly decreased in the benazepril- and MMF-treated groups compared with those of the diabetic group. As expected, the aforementioned indices were markedly lower in the benazepril and MMF combined treatment group than those in the single medication groups. These data suggested that MMF may have a protective role in diabetic nephropathy, and that the underlying mechanism may be partially dependent upon the suppression of the epithelial mesenchymal transition. Furthermore, the combination of benazepril and MMF conferred enhanced efficacy over monotherapies in the treatment of diabetic nephropathy.