血管紧张素1-7预防肺动脉高压右心衰竭发展的实验研究  

The preventive effect of ang-(1-7) on the development of right heart failure induced by pulmonary arterial hypertension in rats

作　　者：吴思婧 郭雯[1] 陈梦娜[1] 李刚[1] 刘巍[1] 龚志忠 周坤[1] 高海[1] 马涵英[1] 

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心内科,100029

出　　处：《心肺血管病杂志》2015年第8期652-656,667,共6页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学青年基金(81200179);北京市卫生系统高层次卫生技术人才培养计划(2013-3-0004)

摘　　要：目的:探讨血管紧张素1-7对大鼠肺动脉高压(PAH)右心衰竭的预防作用。方法:雄性,SD大鼠,30只,随机分为四组,A组为空白对照组(n=6)、B组为PAH右心衰竭组(n=9)、C组为Ang-(1-7)干预组(n=9)、D组为Ang-(1-7)对照组(n=6),饲养6周。超声心动测定心功能,右心导管测定血流动力学参数;处死后测量右心室肥厚指数(RVHI),天狼星红染色计算心肌组织胶原容积分数(CVF);酶联免疫吸附实验(ELISA)测定血浆及右心室心肌血管紧张素II(Ang II)含量,Western Blot测定右心室心肌信号通路分子表达。结果:超声心动检查提示与PAH右心衰竭组相比,Ang-(1-7)干预组4周时RVEDD、RVWT显著降低,RVEF显著提高。ELISA结果提示与PAH右心衰竭组相比,Ang-(1-7)干预组血浆Ang II水平降低。病理染色提示与PAH右心衰竭组相比,Ang-(1-7)干预组CVF值显著降低。WB结果提示与PAH右心衰竭组相比,Ang-(1-7)干预组右心室心肌AT1R、Egr-1表达均显著降低。结论:PAH右心衰竭大鼠循环及右心室局部存在肾素血管紧张素系统(RAS)过度激活,血管紧张素1-7可能减缓肺动脉高压右心衰竭。Objective：To investigate the effect of angiotensin-（1-7） [ang-（1-7）] on the development of right heart failure induced by pulmonary arterial hypertension （PAH）. Methods： 30 male Sprague-Dawley rats were randomly divided into 4 groups： control group, right heart failure group（ RHF）, RHF ＋ ang-（1-7） group and Ang-（1-7） control group. Rats underwent echocardiography at 4 weeks and 6 weeks to assess disease progression. At 6 weeks, pulmonary catheterization was performed at the sacrifice of animals. Cardiac pathology and the levels of ang II in serum and right ventricles were detected. Expression of AT1R, TGF-[31, ERK1/2, p-ERK1/2 and Egr-1 was also measured by Western blotting. Results：Echocardiography revealed that Ang-（ 1- 7） intervention improved right ventricular ejection fraction （RVEF） significantly. The elevated plasma ang II level was dramatically decreased in Ang-（1-7） treated rats. Ang-（1-7） rats showed declined expression of AT1R and Egr-1 comparing with RHF rats. Conclusion： Ang-（1-7） could prevent the progress of right heart failure caused by pulmonary arterial hypertension.

关 键 词：肺动脉高压 右心衰竭 血管紧张素1-7 血管紧张素转化酶2 

分 类 号：R54[医药卫生—心血管疾病]