摘要
目的:探讨血管紧张素转化酶2(ACE2)激活,对肺叶切除联合野百合碱注射,诱导重度肺动脉高压(PAH)的预防作用。方法:左肺切除+野百合碱注射建立大鼠重度PAH模型。雄性SD大鼠50只,随机分为5组,A组为空白对照组、B组为Resorcinolnaphthalein(Res)对照组,C组为PAH组,D组为Res预防组,E组为Res+A-779干预组。测量平均肺动脉压力(mPAP)、右心室肥厚指数(RVHI);弹力纤维染色分析肺血管病变;ELISA、Western Blot分析肾素血管紧张素系统各主要成分的水平。结果:处理3 w后,C组大鼠mPAP、RVHI明显升高,出现了严重的肺动脉中膜肥厚、内膜增生(与A组比较,P<0.05),D组上述4项指标明显减轻(与C组比较,P<0.05);E组则比D组病变严重(P<0.05)。ACE、Ang-II及AT1R水平,D组明显低于C组(P<0.05),而ACE2、Ang-(1-7)及Mas水平D组明显高于C组(P<0.05)。结论:Res激活ACE2可以抑制重度肺动脉高压的形成,调节肾素血管紧张素系统的平衡,可能是其作用的主要机制之一。
Objective：To investigate the effect of angiotensin converting enzyme 2（ACE2） activation by resorcinolnaphthalein（Res） on the severe pulmonary arterial hypertension（PAH） in rats.Methods：The pulmonary arterial hypertension in rats was induced by monocrotaline injection one week following left pneumonectomy.Fifty male rats were randomly divided into five groups including control（Group A）,Res-treated normal rats（Group B）,PAH group（Group C）,Res-treated PAH rats（Group D） and combined treated with Res and A-779 group（Group E）.The mean pulmonary arterial pressure（mPAP）,systolic arterial pressure,right ventricular hypertrophy index（RVHI）,medial hypertrophy and neointimal formation in pulmonary arteries with different diameter and the levels of main renin-angiotensin-system components in lungs were examined in the rats.Results：Three weeks after the treatment,ACE2 activity increased in Group B when compared to Group A（P0.05）,and the values in group D were higher than group C（P0.05）.The rats in group C showed high mPAP,RVHI,severe medial hypertrophy and neointimal formation when compared to Group A（P0.05）.These four index in group D were significantly lower than the values in group C（P0.05）,but were not changed in Group E.Compared to group C,group D rats displayed lower levels of ACE,Angiotensin-II and AT1R（all P0.05）,but higher levels of ACE2,angiotensin-（1-7） and Mas（all P0.05）.Conclusion：Activation of ACE2 by Res continuous injection prevented the formation of severe PAH through mediating the balance among the components of renin-angiotensin-system.
出处
《心肺血管病杂志》
CAS
2012年第2期192-195,共4页
Journal of Cardiovascular and Pulmonary Diseases
基金
国家自然科学基金项目(30972958)
关键词
肺动脉高压
血管紧张素转化酶2
内膜增生
Pulmonary arterial hypertension
Angiotensin converting enzyme 2
Neointimal formation
