奥美沙坦对心力衰竭大鼠肺脏肾上腺素能受体表达的影响

目的:研究奥美沙坦对心力衰竭大鼠肺脏α1A-肾上腺素受体(α1A-AR)和β1、β2肾上腺素受体(β-AR)表达水平及对血浆肾素活性(plasma rennin activity,PRA)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)水平的影响。方法:45只Wistar大鼠随机分为正常对照组(A组)、假手术组(B组)、心力衰竭模型对照组(C组)和奥美沙坦组(D组),采用灌胃法给药。超声心动图检测用药前后大鼠心脏功能,灌胃治疗8 w后,腹主动脉取血,采用放射免疫法测定各组大鼠PRA、AngⅡ水平,取大鼠肺组织,采用蛋白质免疫印迹法(Western Blot)测定各组的α1A-AR、β1-AR和β2-AR的蛋白表达水平。超声心动图检测用药前后大鼠心脏功能。治疗8 w后,腹主动脉取血,采用放射免疫法测定各组大鼠PRA、AngⅡ水平,取大鼠肺组织,采用蛋白质免疫印迹法(Western Blot)测定各组的α1A-AR、β1-AR和β2-AR的蛋白表达水平。结果 :用药前A组与B组比较,大鼠左心室射血分数(LVEF)组间差异无统计学意义(P>0.05);与B组比较,C组、D组大鼠LVEF明显降低(均P<0.05)。用药后,与C组比较,D组LVEF显著改善(P<0.05)。用药后,A组与B组大鼠PRA、AngⅡ水平差异无统计学意义(P>0.05);与B组比较,C组大鼠PRA、AngⅡ水平明显升高(P<0.01);与C组比较,D组大鼠血浆PRA、AngⅡ水平明显降低(P<0.05);在蛋白质表达水平,A组与B组用药后比较,各受体水平差异无统计学意义(P>0.05)。与B组比较,C组大鼠α1A-AR、β1-AR表达水平显著下调(P<0.05),β2-AR表达水平明显上调(P<0.01);与C组相比,D组α1A-AR、β1-AR及β2-AR水平均显著升高(均P<0.05)。结论:奥美沙坦能够改善心肌梗死后心力衰竭大鼠的心脏功能,提高LVEF,同时能够降低心力衰竭时血浆中升高的PRA和AngⅡ,并使心力衰竭大鼠肺脏下调的α1A-AR、β1-AR上调,表达增加的β2-AR进一步上调。奥美沙坦对慢性心力衰竭(chronic heart failure,CHF)时交感-肾上腺素系统激活后肾上腺素受体表达的调节作用和对PRA、AngⅡ的抑制作用,有利于维持心力衰竭时肺脏的通气/血流比值,减轻肺水肿,改善心力衰竭时的肺循环淤血,对CHF的肺脏起到了有益的保护作用。

Effects of olmesartan therapy on the expression of the lung adrenergic receptors in the chronic heart failure rats

Objective:To investigate the effect of Olmesartan on the levels of plasma rennin activity(PRA),plasma angiotensin Ⅱ(Ang Ⅱ) and the protein levels of f α1A,β1 andβ2 adrenergic receptors(AR) in lungs from rats with chronic heart failure(CHF) induced by myocardial infarction.Methods: Models of CHF were established by anterior descending coronary artery ligature.Forty five Wistar rats were randomly divided into four groups: control group(Group A),sham operation group(Group B),CHF model group(Group C),Olmesartan group(Group D).The cardiac functions before and after therapy were tested by echocardiography.After 8w of therapy,PRA and Ang Ⅱ levels were measured by radioimmunoassay.The protein expression levels of α1A-AR,β1-AR andβ2-AR in lungs were measured by Western blot.Results: The left ventricle ejection factions(LVEF) had no significant differences between A and B(P>0.05).Compared with B,the LVEF of C and D were dramatically decreased before therapy(P<0.05).After treat with Olmesartan,compared with C,LVEF of D was obviously improved(P<0.05).The levels of PRA and Ang Ⅱ of C were higher than B(P<0.01).Compared with C,PRA and Ang Ⅱ of D were significantly decreased(P<0.05).After therapy,the protein expression of α1A-AR,β1-AR and β2-AR in A and B(P>0.05) has no significant difference.Compared with B,α1A-AR,β1-AR protein expression decreased in C(P<0.05),but expression of β2-AR markedly increased in C(P<0.01).Compared with C,protein levels of α1A-AR,β1-AR and β2-AR significantly increased in D(all P<0.05).Conclusion: Olmesartan can improve cardiac function,decline plasma PRA and Ang Ⅱ levels,and upregulate the protein expression of α1A-AR,β1-AR and β2-AR in lungs of CHF rats induced by myocardial infarction.Olmesartan regulates the expression levels of adrenergic receptors in lungs after sympathetic nerve system(SNS) is activated in CHF and reduces the PRA and Ang Ⅱ levels,which are benefit to maintain lung ventilation/perfusion ratio stability,relieve the congestion of pulmonary circulation and reduce pulmonary edema.Olmesartan plays a beneficial role in the protection of lung function in CHF.