氯沙坦钾通过调控ACE2对慢性香烟烟雾诱导的大鼠肺动脉重构的治疗作用  

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary vascular remodeling via angiotensin-converting enzyme-2 in rats

作　　者：韩素霞[1] 唐梅芳[1] 王娟[1] 常建梅[1] 郭李平[1] 冯磊[1] 

机构地区：[1]新疆医科大学第五附属医院心血管内科,乌鲁木齐830000

出　　处：《重庆医科大学学报》2014年第10期1363-1367,共5页Journal of Chongqing Medical University

基　　金：国家自然科学基金资助项目(编号:81060023)

摘　　要：目的:观察慢性香烟烟雾诱导大鼠肺动脉高压的形成,探讨氯沙坦钾通过调控血管紧张素转换酶2(angiotension converting enzyme,ACE2)的表达对大鼠肺动脉高压的治疗作用。方法:将健康雄性SD大鼠48只按析因设计分为对照组、对照+氯沙坦钾组、香烟暴露组和香烟暴露+氯沙坦钾组。香烟暴露组和香烟暴露+氯沙坦钾组大鼠在标准毒理香烟暴露箱中接受被动吸烟,对照组和对照+氯沙坦钾组同时在同种毒理箱中暴露于新鲜空气。氯沙坦钾给药采用每天腹腔内注射,正常对照组给等量生理盐水注射。建立香烟诱导的肺动脉高压大鼠模型后,用插入导管法检测右室收缩压(right ventricular systolic pressures,RVSP);图像分析法观察肺结构变化;放射免疫法检测大鼠肺组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)水平;Western blot分析法检测ACE2的蛋白表达;进一步给予氯沙坦钾干预后检测其对大鼠肺动脉高压的治疗作用。结果:香烟暴露6个月后,香烟暴露组大鼠RVSP升高,肺动脉内膜增生、肺动脉壁明显增厚,管腔狭窄;与对照组相比,肺组织匀桨中AngⅡ含量较对照组明显升高(P<0.05);Western blot法检测肺组织ACE2的蛋白表达水平降低(P<0.05);给予氯沙坦钾干预后,香烟暴露+氯沙坦钾组大鼠肺小动脉重构程度改善,RVSP降低,肺组织AngⅡ含量减少,ACE2蛋白表达增加(P<0.05)。结论:慢性香烟烟雾可诱导肺小动脉重构,甚至肺动脉高压,还可刺激肺组织AngⅡ水平升高和ACE2的蛋白表达减弱。氯沙坦钾通过促使ACE2蛋白表达增加而改善肺动脉高压病程中肺小动脉的重构。氯沙坦钾使ACE2表达升高可能是其对肺动脉高压病程中肺小动脉重构作用机制的一部分。Objective：To determine the effect of losartan on chronic cigarette smoke-induced PAH and its possible mechanism. Methods：Rats were randomly divided into four groups according to the factorial design：A group：control;B group：control plus losar- tan;C group：smoke exposure only;D group：smoke exposure plus losartan. The rats in C and D groups were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. After 6 months,right ventriculus systolic pressure（RVSP） was ex- amined. Tissue angiotensin Ⅱ （Ang Ⅱ ） levels were measured by iodine-125 radioimmunoassay（RIA） and angiotension converting enzyme 2（ACE2） in lung homogenates were measured by Western blot. Results：Elevated RVSP,thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased Ang H and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling,inhibited the smoke-induced RVSP and Ang Ⅱ elevation and partially reversed the ACE2 decrease in rat lungs. Conclusion：The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

关 键 词：血管紧张素转换酶2 香烟烟雾 氯沙坦钾 肺动脉重构 

分 类 号：R542.54[医药卫生—心血管疾病]