ACE2-Ang(1-7)-Mas受体轴在高血压射血分数保留心力衰竭中的作用  

Role of ACE2-Ang(1-7)-Mas receptor axis in heart failure with preserved ejection fraction with hypertension

作　　者：喻江标 吴永港[2] 张银妆[1] 张里程 马琦琳[1] 罗秀菊[3] YU Jiangbiao;WU Yonggang;ZHANG Yinzhuang;ZHANG Licheng;MA Qilin;LUO Xiuju(Department of Cardiology,Xiangya Hospital,Central South University,Changsha 410008;Department of PET/ CT Center,Second Xiangya Hospital,Central South University,Changsha 410011;Department of Laboratory Medicine,Xiangya School of Medicine,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅医院心血管内科,长沙410008 [2]中南大学湘稚二医院PET-CT中心,长沙410011 [3]中南大学湘雅医学院医学检验系,长沙410013

出　　处：《中南大学学报（医学版）》2018年第7期738-746,共9页Journal of Central South University ：Medical Science

基　　金：湖南省科技厅重点研发项目(2015SK2027).

摘　　要：目的:探讨高血压射血分数保留心力衰竭(以下简称心衰)中血管紧张素转化酶(angiotensin converting enzyme,ACE)2、血管紧张素(1-7)[angiotensin(1-7),Ang(1-7)]的变化及ACE2-Ang(1-7)-Mas受体轴在高血压射血分数保留心衰(heart failure with preserved ejection fraction,HFp EF)中的作用。方法:1)入选原发性高血压患者70例,心脏彩超检测左室射血分数(left ventricular ejection fraction,LVEF)≥50%,根据HFp EF的诊断标准将高血压患者分为单纯高血压(hypertension,HBP)组和高血压HFp EF组;同时入选35例健康体检者作为正常对照组(Control)。采用酶联免疫吸附测定法(enzyme linked immunosorbent assays,ELISA)检测各组血浆中ACE2,Ang(1-7),血管紧张素II(angiotensin II,Ang II)及脑利钠肽(brain natriuretic peptide,BNP)水平。2)选取雄性SD大鼠24只,随机选取8只作为假手术组(Sham),16只SD大鼠行腹主动脉缩窄术(abdominal aortic constriction,AAC)建立HFp EF模型组,后将HFp EF模型组SD大鼠随机分为两组(n=8):一组于腹腔内注射Ang(1-7)0.5 mg/(kg.mg)作为Ang(1-7)干预组;另一组于腹腔内注射等剂量生理盐水(AAC组)。干预6周后处死所有大鼠,对心脏标本行苏木精-伊红(hematoxylineosin,HE)染色,采用Western印迹法测定心肌组织中ACE,ACE2及Mas受体蛋白表达水平。结果:HBP组及高血压HFp EF组的BNP和Ang II均较Control组明显增高(P<0.01);HBP组的ACE2,Ang(1-7)与Control组比较,差异无统计学意义(P>0.05),而高血压HFp EF组ACE2和Ang(1-7)较HBP组及Control组均明显升高(P<0.01)。HE染色结果显示A AC组的心肌细胞较Sham组明显肥大,而Ang(1-7)干预组的心肌细胞肥大程度较AAC组减轻,AAC组的ACE2,ACE及Mas受体蛋白表达水平较Sham组均明显升高(P<0.05),Ang(1-7)干预组ACE2和Mas受体表达水平较AAC组明显升高(P<0.05),而ACE表达水平未受影响(P>0.05)。结论:ACE2和Ang(1-7)参与高血压HFp EF的发生发展过程,对高血压HFp EF的心衰和心肌重构的严重�To investigate changes in the angiotensin converting enzyme 2 （ACE2） and angiotensin （1-7） [Ang （1-7）] and to explore the role of ACE2-Ang （1-7）-Mas receptor axis in hypertension with heart failure with preserved ejection fraction （HFPEF）. Methods： A total of 70 patients with primary hypertension and preserved left ventricular ejection fraction （LVEF〉50%） were recruited and patients were divided into a hypertension group （HBP） and a heart failure with preserved ejection fraction group （HFpEF） according to the diagnostic criteria of HFpEF. Thirty-five healthy participants were selected randomly as a control group. Enzyme linked immunosorbent assays （ELISA） method was used to detect concentration of Ang （1-7）, ACE2, angiotensin II （Ang II）, brain natriuretic peptide （BNP） in plasma. Male Sprague-Dawley （SD） rats was randomly divided into 2 groups： An HFpEF group （n=16） and a sham group （n=8）. Rats （n=8） in the AAC group were given Ang （1-7） [0.5 mg/（kg.d）, intraperitoneally] for 6 weeks, and the rest were given equal dose normal saline. Then all the rats were killed, and the hearts were taken out for hematoxylineosin （HE） staining. The protein expressions of angiotensin converting enzyme （ACE）, ACE2, and Mas receptor were detected by Western blot. Results： The BNP and Ang II were significantly increased in the HBP group and the HFpEF group compared with the control group （P〈0.01）. There were not significantly different in levels of ACE2 and Ang （1-7） between the HBP group and control group （P〉0.05）, whereas those levels were significantly increased in the HFpEF group compared with the HBP group and control group （P〈0.01）. HE staining showed obvious hypertrophy of myocardial cell in the AAC group compared with the sham group. Hypertrophy of myocardial cell in the AAC＋Ang （1-7） group was significantly higher than that in the AAC group. Expressions of ACE, ACE2, and Mas receptor proteins were significan

关 键 词：高血压 射血分数保留心力衰竭 ACE2-Ang(1-7)-Mas受体轴 心肌重构 

分 类 号：R541.6[医药卫生—心血管疾病]