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Metformin exerts renoprotective effect by reducing proteinuria in spontaneously-hypertensive rats
Abstract
Purpose: To study the mechanism involved in metformin (DMBG)-induced reduction of albuminuria in spontaneously-hypertensive rats (SHRs).
Methods: The SHRs were divided into DMBG SHR group (n = 30) given DMBG (300 mg/kg) and NC SHR group (n = 10) given distilled water (2 ml/day), while Wistar-Kyoto rats (WKY) rats were divided into DMBG WKY group (n = 30) given DMBG (300 mg/kg ) and NC WKY group (n = 10) administered distilled water (2 ml/day). Urinary protein levels were measured and compared. Inflammatory infiltration in renal tissue, and expression of vascular endothelial growth factor (VEGF) were assessed. Abdominal aortic blood was used to measure serum levels of creatinine and blood urea nitrogen (BUN).
Results: Urinary protein was markedly elevated in SHRs, while BUN in SHRs was lowered, relative to WKY rats (p < 0.05). Moreover, inflammatory cell population was lower in DMBG SHRs group than in WKY rats (p < 0.05). Kidney expressions of VEGF in SHR and WKY rats treated with metformin were significantly reduced, relative to those in untreated rats, but VEGF-A in DMBG SHR rats was markedly elevated, relative to NC SHR group, and was also raised in DMBG WKY, when compared with NC WKY rats (p < 0.05).
Conclusion: Metformin reduces albuminemia in spontaneously hypertensive rats by up-regulating VEGF expression, thereby exerting renoprotective effect. This finding provides ideas for research and development of other therapeutic approaches.
Keywords: Metformin, Spontaneous hypertension, Renoprotective, Albuminuria, Kidney, Vascular endothelial growth factor (VEGF)