Xiao Xiaoyan, Wang Jie, Chang Xiangdi, Zhen Junhui, Zhou Gengyin, Hu Zhao
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2015 Sep;12(3):4043-4050. doi: 10.3892/mmr.2015.3934. Epub 2015 Jun 15.
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 α‑smooth muscle actin (α‑SMA) and transforming growth factor (TGF)‑β1 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 α‑SMA and TGF‑β1, 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.
近期在动物模型中的研究表明，霉酚酸酯（MMF）对实验性糖尿病肾病具有一定的保护作用。因此，本研究旨在探讨单独或联合使用霉酚酸酯和苯那普利治疗可改善糖尿病肾病这一假说，并在大鼠模型中确定潜在的作用机制。通过单次腹腔注射链脲佐菌素诱导大鼠患糖尿病。随后，大鼠分别接受苯那普利、MMF或两种药物联合治疗，并测定血糖、标准化肾重、尿蛋白和血清肌酐。同时观察肾组织的病理变化。此外，检测上皮-间质转化指标，包括α-平滑肌肌动蛋白（α-SMA）和转化生长因子（TGF）-β1的表达。与未治疗的糖尿病组大鼠相比，接受苯那普利或霉酚酸酯治疗的糖尿病大鼠的标准化肾重、尿蛋白和血清肌酐水平显著改善。肾脏重量增加和尿白蛋白排泄增加的同时检测到肾脏的病理变化，各组间变化趋势相似。此外，与糖尿病组相比，苯那普利和MMF治疗组肾小管间质中上皮-间质转化指标（包括α-SMA和TGF-β1）的表达显著降低。正如预期的那样，苯那普利和MMF联合治疗组的上述指标明显低于单一药物治疗组。这些数据表明，MMF可能对糖尿病肾病具有保护作用，其潜在机制可能部分依赖于对上皮-间质转化的抑制。此外，苯那普利和MMF联合治疗在糖尿病肾病治疗中比单一疗法具有更高的疗效。
