血管紧张素(1-7)在高盐高脂饮食诱导的代谢综合征小鼠肾脏损伤中的作用  

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

作　　者：朱男[1] 韩雅玲[2] 闫承慧[2] 张效林[2] 赵昕[2] 张玉婕[2] 李洋[2] 

机构地区：[1]辽宁医学院研究生院,辽宁锦州121000 [2]沈阳军区总医院心内科,沈阳110840

出　　处：《解放军医学杂志》2013年第10期787-791,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展计划(973计划)项目(2012CB517800)~~

摘　　要：目的采用高盐高脂饮食喂养C57BL/6小鼠建立代谢综合征(MS)模型,探讨血管紧张素转换酶2(ACE 2)及血管紧张素(1-7)[Ang(1-7)]在MS导致的肾脏损伤中的作用。方法 56只SPF级C57BL/6小鼠随机分为7组(每组8只),分别给予正常饮食(ND),高盐(HSD)饮食,高脂(HFD)饮食,高盐高脂(HSFD)饮食,以及分别采用依那普利20mg/(kg·d)+高盐高脂饮食(HSFD-E),缬沙坦50mg/(kg·d)+高盐高脂饮食(HSFD-V),缬沙坦50mg/(kg·d)+Ang(1-7)Mas受体抑制剂A-779 150ng/(kg·d)+高盐高脂饮食(HSFD-VA)。16周后检测血压、体重、血糖及尿蛋白排泄率等基础代谢指标,然后颈动脉取血,ELISA法检测血清中AngⅡ及Ang(1-7)水平,Western blotting检测肾脏中ACE 2及Ⅲ型胶原的表达,HE及Masson染色观察肾脏病理学改变。结果高盐高脂饮食喂养16周后,C57BL/6小鼠血压、内脏脂肪重量与体重比、血脂、血糖以及尿蛋白排泄率等各项代谢指标均明显升高(P<0.05);肾脏出现明显纤维化改变;血清AngⅡ水平升高,Ang(1-7)水平降低(P<0.01);肾脏组织中ACE2表达降低(P<0.05)。给予缬沙坦干预可明显缓解高盐高脂引起的代谢异常,肾脏损伤程度减轻,肾脏和血清中ACE2及Ang(1-7)表达增加(P<0.05)。给予依那普利或缬沙坦+A-779干预后上述指标与未干预组比较均无明显变化。结论应用高盐高脂饮食喂养C57BL/6小鼠可成功建立MS模型。AngⅡ受体1阻滞剂缬沙坦能够缓解高盐高脂导致的代谢异常和肾脏损伤,其对肾脏的保护机制可能与Ang(1-7)表达增加有关。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

关 键 词：代谢综合征X 肽基二肽酶A 血管紧张素Ⅱ1型受体拮抗剂 血管紧张素（1-7） 肾病 

分 类 号：R589[医药卫生—内分泌]