摘要
目的 探讨慢性香烟暴露诱导的肺动脉高压形成过程中ACE、ACE2和血管紧张素Ⅱ(AngⅡ)的调控作用及特异性血管紧张素Ⅱ受体拮抗剂氯沙坦的治疗作用.方法 健康雄性SD大鼠60只,随机分为A组:对照组(Con);B组:30 mg/kg单纯氯沙坦组(30 mg/kg Los);C组:香烟诱导组(SM);D组:香烟诱导+10 mg/kg氯沙坦组(SM+10 mg/kg Los);E组:香烟诱导+30 mg/kg氯沙坦组(SM+30 mg/kg Los).香烟暴露组和香烟暴露+氯沙坦组在标准毒理香烟暴露箱中接受被动吸烟;对照组同时在同种毒理箱中暴露于新鲜空气;氯沙坦给药采用每天腹腔内注射;正常对照组给予等量生理盐水注射.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(RVSP);Western blotting法分析ACE2和ACE的蛋白表达量;放射免疫分析试剂药盒测定肺组织中的AngⅡ表达水平.结果 香烟暴露6个月后,慢性香烟暴露组大鼠RVSP较对照组明显升高,大鼠肺组织中AngⅡ表达水平显著增高.Western blotting结果显示,ACE表达水平增高,香烟暴露组大鼠肺组织ACE2蛋白表达水平降低,而ACE蛋白表达水平较对照组升高.氯沙坦干预治疗后,香烟暴露+氯沙坦组大鼠RVSP和AngⅡ较香烟暴露组降低(P<0.05),肺组织ACE2蛋白表达水平较香烟暴露组增强,ACE蛋白表达水平较香烟暴露组减少(P<0.05).结论 慢性香烟暴露可导致肺动脉高压,还可刺激肺组织ACE2和ACE的蛋白表达变化,提示ACE2和ACE在慢性香烟暴露诱导的肺动脉高压中起一定作用.
Objective Cigarette smoking may induce pulmonary hypertension.The potential role of ACE2 and ACE in cigarette smoke-induced is yet unclear.Methods Rata were randomly divided into five groups:A:control,B:control plus losartan,C:smoke exposure only,D:smoke exposure plus+10 mg/kg losartan,E:smoke exposure plus+30 mg/kg losartan.The C and D groups were exposed to the smoke of 15 commercial cigarettes.After 6 months,right ventricle systolic pressure(RVSP),biochemical changes were examined.Results The RVSP and Ang Ⅱ were raised and the level of lung tissue ACE2 was decreased in cigarette smoke-induced pulmonary hypertension in rata compared with that in control group.The RVSP and Ang Ⅱ were reduced and ACE2 was increased as shown by inhibition with losartan.Conclusion This study demonstrated that ACE2 and ACE played an essential role in smoke-induced pulmonary hypertension.
出处
《中国心血管病研究》
CAS
2014年第4期330-333,383,共5页
Chinese Journal of Cardiovascular Research
基金
国家自然科学基金项目(项目编号:81060023)