Effects of angiotensin (1-7) on nephrosis of the mice with metabolic syndrome induced by high-salt and high-fat diet

Objective To establish a metabolic syndrome model of C57BL/6 mice by high-salt and high-fat diet, and investigate the effects of angiotensin converting enzyme 2 (ACE 2) and angiotensin (1-7) on renal damage in mice. Methods Fifty-six male C57BL/6 mice were randomly divided into 7 groups (8 each), and fed with normal diet (0.3% NaCl, 10% fat), high-salt diet (8% NaCl, 10% fat), high-fat diet (0.3% NaCl, 60% fat), high-salt and high-fat diet (8% NaCl, 60% fat), high-salt and high-fat diet with enalapril 20mg/(kg•d), with valsartan 50mg/(kg•d), and with valsartan 50mg/(kg•d) plus Mas receptor antagonist (A-779) 150ng/(kg•d), respectively for 16 weeks. Basal metabolic index including blood pressure, body weight, blood glucose and urinary albumin excretion rate (UAER) were tested. After intraperitoneal anesthesia with chloral hydrate, the blood was collected from the carotid artery. Serum angiotensin Ⅱ and angiotensin (1-7) levels were detected by ELISA; Western blotting was performed to evaluate the expression of ACE 2 protein and collagen Ⅲ in renal tissue; renal pathological changes were observed by HE and Masson staining. Results The blood pressure, ratio of visceral fat weight/body weight, blood lipid, blood glucose and UAER increased significantly in the C57BL/6 mice fed with high-salt and high-fat diet for 16 weeks, and the renal fibrosis change was obvious, serum angiotensin Ⅱ level increased, expressions of ACE 2 and angiotensin (1-7) decreased significantly in the renal tissue. In different intervention groups, valsartan obviously alleviated the abnormal metabolism, ameliorated renal injury, promoted the expression of ACE2 and angiotensin (1-7) in the kidney and serum. However, no significant change was observed in the groups with intervention of enalapril or valsartan+A-779 compared with non-intervention group. Conclusions High-salt and high-fat diet can be used to successfully establish the model of metabolic syndrome in C57BL/6 mice. Valsartan, an angiotensin Ⅱ receptor blocker, can alleviate the metabolic abnormality caused by the high-salt and high-fat diet, and the protection mechanism may be related to up-regulation of angiotensin (1-7). DOI: 10.11855/j.issn.0577-7402.2013.10.001