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. 2017 Jun;13(6):3223-3230.
doi: 10.3892/etm.2017.4420. Epub 2017 May 4.

VSports - Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway

Yuan Qiao  1 , Ke Gao  2 , Yangwei Wang  1 , Xueliang Wang  3 , Bo Cui  4
Affiliations

Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway (V体育2025版)

Yuan Qiao et al. Exp Ther Med. 2017 Jun.

Abstract

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 VSports手机版. 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. .

Keywords: diabetic nephropathy; p38 mitogen-activated protein kinase/transforming growth factor beta 1 pathway; resveratrol V体育安卓版. .

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Figures

Figure 1.
Figure 1.
Effect of RSV treatment following exposure to high glucose in the mesangial cell line CRL-2573. (A) Relative levels of cell viability among CRL-2573 cells treated with NG, HG, HG + vehicle (DMSO), HG + RSV, or HG + SB. (B) Representative western blot analysis showing p-p38, TGF-β1 and fibronectin expression in CRL-2573 cells treated with NG, HG, HG + vehicle (DMSO), HG + RSV or HG + SB, and the corresponding quantitative data. *P<0.05 vs. NG, #P<0.05 vs. HG. NG, normal glucose; HG, high glucose; RSV, resveratrol; DMSO, dimethyl sulfoxide; SB, SB-203580; p-p38, phosphorylated-p38; TGF-β1, transforming growth factor beta 1; FN, fibronectin.
Figure 2.
Figure 2.
Hematoxylin and eosin staining of kidney sections from diabetic rats with and without RSV treatment. (A) Normal glomerulus and tubules of an NG rat. (B) Glomerulus and tubules of a DM rat. Glomerular thickening, interstitial fibrosis and hyaline changes, epithelial cellular vacuolar degeneration, hyaline casts and arteriolopathy are visible. (C) Glomerulus and tubules of a DM rat treated with DMSO vehicle control. Histological alterations of glomeruli and arterioles are similar to those observed in the DM group. (D) Glomerulus and tubules of a DM rat treated with RSV. Milder histological alterations of glomeruli and arterioles are observed. Magnification, ×400. NG, normal control group; DM, diabetes mellitus control group; DM + DMSO, diabetic rats treated with vehicle; DM + RSV, diabetic rats treated with RSV. The dark blue color represents the nuclei and the pink color represents cytoplasm, fibronectin and red blood cells.
Figure 3.
Figure 3.
Immunohistochemical staining of kidney sections from diabetic rats with and without RSV treatment. Kidney sections from rats in each experimental group were examined by immunohistochemical staining for p-p38, p38, TGF-β1 and fibronectin (magnification, ×400). Quantitative relative density data are shown on the right. NG, normal control group; DM, diabetes mellitus control group; DM + DMSO, diabetic rats treated with vehicle; DM + RSV, diabetic rats treated with RSV; p-p38, phosphorylated-p38; TGF-β1, transforming growth factor beta 1; FN, fibronectin. *P<0.05 vs. NG, #P<0.05 vs. DM. The blue color represents nuclei and the brown color represents the assessed protein.
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