长效硝酸酯对心力衰竭大鼠心脏血管紧张素Ⅱ受体表达水平的影响  

The effect of long-acting nitrate therapy on the expression of Angiotensin Ⅱ receptors of myocardium in rats with heart failure

作　　者：陈萌萌[1] 李艳芳[1] 彭余波 

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所急诊危重症中心,100029

出　　处：《心肺血管病杂志》2015年第1期57-61,共5页Journal of Cardiovascular and Pulmonary Diseases

基　　金：中国医师协会探索心血管研究基金项目(DFCMDA201203)

摘　　要：目的:探讨长效硝酸酯(异乐定)对心肌梗死后慢性心力衰竭(CHF)大鼠心功能、血浆肾素活性(plasma renin activity,PRA)和血管紧张素II(Angiotensin II,Ang II)水平以及非梗死区左心室组织血管紧张素II受体(Angiotensin II receptor,ATR)各亚型表达水平的影响。方法:选用雄性Wistar大鼠,随机分为正常对照组(N组)、假手术组(SH组),结扎左冠状动脉前降支制作心肌梗死后心力衰竭模型,分为心力衰竭模型组(HF组)、硝酸酯小剂量组(LN组)、硝酸酯大剂量组(HN组)、阳性药物对照组(奥美沙坦酯,OL组)及硝酸酯大剂量联合阳性药物组(HN+OL组),灌胃法给药6周。超声心动图检测用药前后心功能,放射免疫法检测血浆PRA、Ang II水平,RT-PCR和Western blot检测各组心肌AT1R及AT2R的表达水平。结果:1用药后,与HF组相比,HN组、OL组和HN+OL组左心室射血分数(LVEF)显著升高(P<0.05);与OL组相比,HN+OL组LVEF显著升高(P<0.05)。2与SH组相比,HF组PRA、Ang II水平显著升高(P<0.01),AT2R表达水平明显上调(P<0.05),AT1R表达水平明显下调(P<0.05);与HF组相比,HN、OL和HN+OL组PRA、Ang II水平均显著下降(P<0.05、P<0.01),AT2R表达明显下调(P<0.05),AT1R表达明显上调(P<0.05);与OL组相比,HN+OL组AT1R显著上调,AT2R显著下调(P<0.05)。结论:应用长效硝酸酯能降低CHF循环中PRA、Ang II水平,同时使CHF心脏AT1R、AT2R的表达水平反向调节趋于正常,并提高LVEF,显著改善了心功能。大剂量硝酸酯的疗效明显优于小剂量,并可协同奥美沙坦改善心功能。Objective：To investigate the effect of long-acting nitrate （Elantan） on left ventricular func- tion, plasma renin activity （PRA） and angiotensin II （Ang II） plasma levels, and the expression of Ang I1 re- ceptors （ATR） of myocardium on both the mRNA and protein levels in rats with myocardial infarction-induced chronic heart failure （CHF）. Methods：Inbred male Wistar rats were randomly divided into normal control group （group N）, sham-operating group （group SH） and heart failure （HF） model group. The HF model was induced by the ligation of left anterior descending （LAD） artery. Four weeks after the operation, rats with HF were randomly divided into 5 groups： HF group （group HF）, low dose nitrate group（ group LN）, high dose ni- trate group （group HN）, positive medicine （Olmesartan） control group （group OL） and high dose nitrate com- bined with positive medicine group （ group I-IN ＋ OL）. The medication was given by gastric gavage for 6 weeks. Cardiac function was examined by echocardiography before and after the treatment, PRA and AngII plasma lev-els were tested by radio-immunity, the non-infarct left ventricular myocardium were divided to measure the lev- els of ATl R and AT2R using RT-PCR and western blot. Results：After the treatment, LVEF of group HN, OL, and HN ＋ OL markedly increased comparing with that of group HF （P 〈 0. 05）. LVEF was higher in group HN ＋ OL than in group OL（P 〈0. 05）. Compared with group SH, the PRA and Ang II plasma levels were significantly increased （ P 〈 0. 01 ）, the expression of AT2 R was significantly up-regulated （ P 〈 0.05 ）, and the expression of ATt R was down-regulated in group HF （P 〈 0. 05 ）. Compared with group HF, PRA and AngII plasma levels were significantly decreased （P 〈 0. 05 ,P 〈 0.01 ） , the expression of AT2R was significantly down-regulated, and the expression of ATl R was significantly up-regulated in group HN, OL, and HN ＋ OL （P 〈 0.05）. Furthermo

关 键 词：心力衰竭 长效硝酸酯 血管紧张素受体 动物实验 大鼠 

分 类 号：R54[医药卫生—心血管疾病]