Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway.
Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway.
复制标题
白藜芦醇通过 p38 MAPK/TGF-β1 通路的负调节改善大鼠糖尿病肾病
DOI：
10.3892/etm.2017.4420
复制
发表时间：
2017-06
影响因子：
2.7
通讯作者：
Cui B
中科院分区：
文献类型：
--
作者：
Qiao Y;Gao K;Wang Y;Wang X;Cui B
白藜芦醇（RSV）已被证明对糖尿病肾病具有肾脏保护作用，但其潜在机制尚未完全阐明。本研究的目的是探讨RSV在体外大鼠系膜细胞和糖尿病肾病大鼠模型中的治疗作用的机制。在高糖、有或无RSV处理下，评估CRL-2573大鼠系膜细胞的活力及其p38、磷酸化（p）-p38、转化生长因子β 1（TGF-β1）和纤连蛋白的表达水平。糖尿病肾病也诱导Sprague-Dawley大鼠链脲佐菌素治疗。8周时，比较对照组和RSV 20 mg/kg/d治疗组大鼠肾脏的基本生化指标和组织病理学异常以及p38、p-p38、TGF-β1和纤维连接蛋白的表达。在肾小球系膜细胞系中，RSV通过显著降低p38丝裂原活化蛋白激酶（MAPK）活性和TGF-β1表达，抑制高糖诱导的细胞活力和纤维连接蛋白表达的增加（P<0.05）。与对照组相比，RSV可显著降低糖尿病大鼠血糖、血肌酐、尿白蛋白水平，降低肾重和肾重/体重比值（P<0.05）。RSV还可减轻糖尿病大鼠肾脏组织学改变，下调糖尿病大鼠肾脏p-p38、TGF-β1和纤维连接蛋白的表达。这些数据表明，RSV保护肾组织免受糖尿病诱导的损伤，这种活性可能是通过抑制p38 MAPK/TGF-β1信号通路。
Resveratrol (RSV) has been shown to have a renoprotective effect against diabetic nephropathy, but the underlying mechanisms of this have not been fully elucidated. The aim of the current study was to explore the mechanisms responsible for the therapeutic effects of RSV in rat mesangial cells in vitro and in a rat model of diabetic nephropathy. The viability of CRL-2573 rat mesangial cells and their expression levels of p38, phosphorylated (p)-p38, transforming growth factor beta 1 (TGF-β1) and fibronectin were assessed in response to treatment with high glucose, with or without RSV. Diabetic nephropathy was also induced in Sprague-Dawley rats by streptozotocin treatment. At 8 weeks, basic biochemical parameters and histopathological abnormalities as well as the expression of p38, p-p38, TGF-β1 and fibronectin in rat kidneys were compared between control diabetic rats and those treated with 20 mg/kg RSV daily for 4 weeks. In the mesangial cell line, RSV inhibited high glucose-induced increases in cell viability and fibronectin expression by significantly reducing p38 mitogen-activated protein kinase (MAPK) activation and TGF-β1 expression (P<0.05). In diabetic rats, RSV significantly decreased blood glucose, serum creatinine and urinary albumin levels, as well as the kidney weight and ratio of kidney weight/body weight compared with the control group (P<0.05). Moreover, RSV ameliorated renal histological changes and downregulated the expression of p-p38, TGF-β1 and fibronectin in the kidneys of diabetic rats. These data suggested that RSV protected renal tissue from diabetes-induced injury and that this activity may be via inhibition of the p38 MAPK/TGF-β1 signaling pathway.