Diabetic nephropathy (DN) is the major cause of end-stage renal disease. Resveratrol has been shown to ameliorate hyperglycemia in diabetic rats. However, the effects of resveratrol on DN remain unknown. The aim of the present study is to investigate the effects of resveratrol on early-stage DN. Diabetes was induced by streptozotocin injection in male Wistar rats. The diabetic rats were treated with resveratrol at a dose of 20 mg/kg body weight for 8 weeks. Plasma glucose, creatinine, kidney/body weight ratio, and 24-h urinary protein were determined. The renal pathological changes were examined with periodic acid Schiff staining, and renal mesangial cells were cultured in high glucose concentrations with indicated concentrations of resveratrol (2.5, 5.0, and 10.0 μmol/L). The proliferation of mesangial cells was evaluated by methylthiazoletetrazolium assay. Expressions of glutathione S-transferases Mu (GSTM) and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected by western blot, and apoptosis was analyzed using a flow cytometer. Resveratrol reduced plasma glucose, creatinine, and urinary protein excretion, and attenuated renal hypertrophy. Moreover, resveratrol also reduced the expression of GSTM in diabetic rats. In vitro , resveratrol inhibited the proliferation of mesangial cells caused by high glucose and down-regulated GSTM and Nrf2 expressions in a dose-dependent manner. These findings suggest that resveratrol help prevent the progression of DN. The renoprotection by resveratrol is in part mediated through the inhibition of high glucose-induced rat mesangial cell proliferation and downregulation of GSTM expression.

Ntaining 33mM glucose. The cells were divided into the following groups: (1) normal glucose group as control incubated in Roswell Park Memorial Institute (RPMI) 1640 containing 5mM glucose; (2) Ang-(1–7), 10nM, incubated in RPMI 1640 containing 5mM glucose; (3) the HG group incubated in RPMI 1640 containing 33mM glucose; and (4) Ang-(1–7), 10nM, incubated in HG group incubated in RPMI 1640 containing 33mM glucose. After a period of 24 hours, mitochondrial fission and podocyte fusion were observed by electron microscope. Additionally, p53 and Drp1 were tested by Western blot, the position of Drp1 was detected by immunofluorescence, and miR-30a was analyzed by quantitative real-time polymerase chain reaction. Results Ang-(1–7) inhibited mitochondrial fission in HG-treated podocytes. However, Ang-(1–7) also significantly reduced the expression of Drp1 and p53, and improved the expression of miR-30a in HG-induced podocytes. Conclusion Ang-(1–7) inhibited mitochondrial fission in HG-induced podocytes by upregulation of miR-30a and downregulation of Drp1 and p53....

Diabetic nephropathy (DN) is one of the major causes of end‑stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are known to act as antioxidants. The current study aimed to determine the effects of GSPE on the streptozotocin (STZ)‑induced diabetic rat model and to explore the underlying mechanism of its action. Wistar rats were induced into a diabetic state by injection of STZ and were treated with 250 mg·kg‑1·day‑1 GSPE for 24 weeks. Kidney samples were collected for observation of renal pathological changes by light microscope (periodic acid‑Schiff staining) and electron microscopy. Reverse transcription‑polymerase chain reaction, western blotting, and immunohistochemical staining were used to detect the mRNA and protein expression of the receptor for advanced glycation end‑products (RAGE), nephrin and podocin. The results indicated that diabetic rats treated with GSPE had markedly reduced Ccr, urinary albumin excretion, ratio of kidney weight to body weight, AGEs and ECM accumulation (P<0.01) compared with that in the diabetic rats. GSPE treatment can also reverse the renal pathological damage in diabetic rats. Further results indicated that GSPE treatment significantly decreased the RAGE expression level (P<0.01), and significantly increased the expression level of nephrin in the kidney and glomeruli of diabetic rats (P0.05). In conclusion, the results demonstrated that GSPE exerts a reno‑protective effect by decreasing urinary albumin excretion and reversing renal pathological damage in diabetic rats. The underlying mechanism of GSPE activity is associated with the decreased expression of the AGEs/RAGE axis and the increased expression of nephrin in diabetic rats.