心脏β1和M2受体自身抗体与心力衰竭相关性的研究

Autoantibodies against the myocardial β1-adrenergicand M2-muscarinicreceptors in patients with congestive heart failure

目的:本研究拟对不同心脏病所致的心力衰竭(CHF)患者,检测心脏β1和M2受体的自身抗体,探讨心功能发生病理变化时,这两种自身抗体的产生与疾病发生、发展的相关性。方法:以细胞外第2环表位肽段的合成肽作为抗原,应用酶联免疫吸附测定(ELISA)技术,随机检测265例受试者血清中心脏β1和M2受体的自身抗体。结果:CHF组β1受体自身抗体的阳性率为45.7%(86/188),明显高于对照组的10.4%(8/77)(P<0.01);CHF组M2受体自身抗体的阳性率为49.5%(93/188),明显高于对照组的11.7%(9/77)(P<0.01);心功能Ⅱ-Ⅲ级(NYHA心功能分级)的患者自身抗体的阳性率及抗体滴度明显高于Ⅳ级;CHF组β1受体自身抗体阳性血清中高达56.1%的患者同时具有M2受体的自身抗体。结论:心脏β1和M2受体自身抗体存在于多种心脏病所致心力衰竭患者的血清中,可能与心力衰竭时心肌结构变化和功能下降有关;β1和M2受体的双抗体阳性可能是自身免疫反应的多重性表现,提示免疫学机制参与心力衰竭和/或心肌重构的病理生理过程,参与的程度在疾病的早、中期大于晚期。

Objective： To determine whether autoantibodies against β1-adrenergic and M2-muscarinic receptors are related to patients with conge stive heart failure（CHF）.Methods： Both synthetic peptides corresponding to amino acids sequence 197-222 and 169-173 of the second extracellular loops of the β1 and M2 receptors were used as antigens to screen sera from 265 patients.Results： Positive sera for β1-adrenergic receptor was found in 45.73 %（86/188） of CHF patients,while in the controls it was 10.14 %（8/ 77）（P〈 0.01）;positive sera for M2-muscarinic receptor in CHF patients was found in 49.5 %（99/188）,while in the control it was 11.7 %（9/ 77）（P〈 0.01）.The positive ratio of autoantibodies against β1-adrenergic and M2-muscarinic receptors in CHF patients with cardiac function Class Ⅱ-Ⅲ（NYHA） were significantly higher than cardiac function class Ⅳ.The average titer of autoantibodies against β1-adrenergic and M2-muscarinic receptors of the former was significantly higher than the latter;56.1 % of patients with autoantibodies against β1-adrenergic receptor had autoantibodies against M2-muscarinic receptor.Conclusion：Autoantibodies against β1-adrenergic receptor and M2-muscarinic receptor were found in sera from heart failure patients with different cardiac diseases.We propose that autoantibodie s against β1 and M2 receptors are not only related to the IDCM,but also to cardiac structural and functional changes.