心力衰竭大鼠肺脏α1A及β1、β2肾上腺素受体表达的改变

摘要

Objective To invesligale the prolein levels of α1A, β1 and β2 adrenergic receplor (AR ) in lungs of rats with chronic heart failure (CHF) induced by myocardial infarclion. Methods Models of CHF established by anlerior descending coronary artery ligalure. Thirly five Wislar rats were randomly divided into three groups, conlrol group (group A) , sham operalion group (group B) and CHF model group (group C) . The prolein expression levels of α1A-AR, β1-AR and β2-AR in lung lissue were measured by Western blolling. Results Compared with sham operalion group, α1A-AR, β1-AR prolein expression in group C markedly decreased (P <0. 01 and P <0. 05) , expression of β2-AR remarkably increased (P <0. 05) , while there was no significanl difference between conlrol group and sham operalion group (P>0. 05) . Conclusion CHF rats always had pulmonary congeslion, the α1A-AR down-regulation helped pulmonary vascular relax and inhibited smooth muscle cells proliferation, which was a compensation of the pathological situation of CHF lung. Increasing expression of β2-AR in CHF lungs could relax the vascular and bronchial smooth muscle; promote the clearance of pulmonary edema fluid and lung conditions through opening the sodium ion channels and other mechanisms. It could also improve the permeability of the capillaries in lungs. The expression of β1-AR in CHF rats was down-regulated for negative feedback regulation of activation of the sympathetic adrenergic system or compensation of up-regulation of β2-AR, which could maintain a relatively stable rates of alveolar fluid clearance.%目的 研究慢性心力衰竭(chronic heart failure,CHF)时肺脏α1A-肾上腺素受体(α1A-AR)和β1、β2肾上腺素受体(β-AR)表达水平的变化.方法 结扎Wistar大鼠左冠状动脉前降支制作心肌梗死后心力衰竭模型,模型成功后采用数字表法随机分为正常对照组、假手术组和心力衰竭模型组.取大鼠肺组织,采用蛋白质免疫印迹法(Western blotting)分别测定3组的α1A-AR和β1、β2-AR蛋白表达水平.结果 心力衰竭模型组与假手术组相比,α1A-AR、β1-AR的蛋白表达水平显著下调(P<0.01或P<0.05),β2-AR的蛋白表达水平显著上调(P<0.05),正常对照组α1A-AR、β1-AR和β2-AR的蛋白表达水平与假手术组相比差异无统计学意义(P>0.05).结论 CHF大鼠肺循环淤血,α1A-AR下调,有利于肺血管舒张,抑制平滑肌增生以代偿这种病理改变.肺脏β2-AR表达水平上调可能与β2-AR激动可以舒张血管和支气管平滑肌作用,开放钠离子通道等机制促进肺水肿液的清除、并能改善心力衰竭条件下肺脏微血管的通透性有关.心力衰竭时肺脏β1-AR的下调一方面与CHF时交感肾上腺素系统激活产生的负反馈调节有关,另一面可能与代偿性拮抗β2-AR的上调,维持相对稳定的肺泡液体清除率有关.