抗血管紧张素Ⅱ-1型受体的抗体对大鼠心脏活动的影响

Effects of antibody against angiotensin-Ⅱ type 1 receptor on cardiac activities in rats

目的探讨抗血管紧张素Ⅱ-1型受体（AT1）的抗体对大鼠心室肌细胞胞浆钙离子浓度和心功能的影响。方法按照人AT1受体细胞外第二环表位肽段合成AT1受体抗原肽段，以此肽段对大鼠进行主动免疫，获取抗AT1受体抗体；利用CCD钙离子成像系统实时记录细胞内游离钙含量的变化；在离体灌流心脏上，应用生物信号采集系统检测左心室各项心功能指标的变化。结果抗AT1受体抗体可剂量依赖性地增加心室肌细胞内游离钙的浓度，而阴性抗体组则无此作用。抗AT1受体抗体对离体灌流心脏的收缩和舒张功能均有剂量依赖性的增强效应；血管紧张素-Ⅱ也显示有与抗AT1受体抗体相似的生物效应，而且二者对心脏的生物效应均可被AT1受体拮抗剂losartan所阻断。结论抗AT1受体抗体对心肌细胞游离钙含量和心功能具有显著的激动剂样效应，这可能是该抗体参与心脏疾患发病的机制之一。

Objective To clarify the role of anti-AT1-receptor antibody （AT1-R Ab） in the pathogenesis of cardiac diseases, the effects of AT1-R Ab on eardiomyocyte cytosolic Ca2＋ content and cardiac function were studied. Methods The anti-ATe-receptor antibody was derived by immunizing rats with synthetic peptide corre- sponding to the sequence of the second extracellular loop of human AT1 receptor. The cardiomyoeyte eytosolie Ca2＋ content was measured by using CCD ionic imaging system. The left ventricular function of isolated rat heart was detected by using electrophysiological apparatus. Results AT1-R Ab dose-dependently increased the cardiomy- ocyte cytosolic Ca2＋ content. Both systolic and diastolic functions of the isolated perfused rats heart were enhanced by AT1-R Ab in a dose-dependent manner. Ang-Ⅱ, an agonist of AT1 receptor, showed similar effects as those of AT1-R Ab. Moreover, the effects of both AT1-R Ab and Ang-Ⅱ could be blocked by losartan, a specific antagonist of AT1 receptor. Conclusion AT1-R Ab displayed remarkable agonist-like activities via stimulation of AT1-R showing increased effects on cardiomyocyte cytosolic Ca2＋ content and myocardial contractility. This may serve as one of the mechanisms involved in the pathogenesis of cardiac diseases.