乙型肝炎病毒诱导小鼠抗β_1-肾上腺素能受体抗体的致心律失常作用机制

Mechanism of arrhythmias caused by autoantibodies against β_1-adrenoceptors induced by hepatitis B virus in mice

目的:探索乙型肝炎病毒诱导的抗β1-肾上腺素能受体抗体致病作用及机制。方法:乙型肝炎病毒4次接种小鼠(n=30),并记录心电图。ELISA法检测抗体,光镜下观察心肌和肝脏的病变。免疫荧光显示该抗体与豚鼠心肌细胞能否结合。辛酸提取法提纯小鼠IgG。膜片钳技术观察抗体对豚鼠心肌细胞电生理特性的影响。结果:小鼠该抗体的产生与乙型肝炎病毒接种有关。实验小鼠心脏和肝脏未出现明显的组织病理改变,但6只小鼠可出现束枝传导阻滞、窦性停博、室性早搏等心律失常,其抗体均阳性。免疫荧光显示抗体能与豚鼠心肌细胞结合。该抗体使APD20、APD50、APD90分别延长36.46%、29.63%和12.40%,且使L型钙电流峰值增加(49.67±16.01)%。结论:乙型肝炎病毒诱导小鼠产生的抗β1-肾上腺素能受体抗体可导致多种心律失常的发生,该抗体介导心肌细胞L型钙电流增加可能是其致心律失常的机制之一。

AIM: To investigate the significance of autoantibodies against β_1-adrenoceptors induced by hepatitis B virus in the pathogenesis of hepatitis virus myocarditis. METHODS: 30 mice were injected peritoneally with an emulsion of hepatitis B virus and complete Freund's adjuvant every three weeks. The autoantibodies were examined by ELISA, the heart and liver specimens were collected on 56 d for pathological observation and the binding of the autoantibodies to guinea pig cardiac myocytes were examined by immunofluorescence. Using the patch clamp technique, the effects of (1∶50) autoantibodies purified by octanoic acid extraction on the action potential and L type Ca^(2+) currents of guinea pig cardiac myocytes were also investigated. RESULTS: There was a good correlation between the autoantibodies and hepatitis B virus. Without pathological changes in the heart and liver specimens, 6 mice of the test group manifested bundle branch block, sinus arrest and premature ventricular beat etc, which were positive in the autoantibodies. The specific binding of the autoantibodies of the mice to guinea pig cardiac myocytes was observed. (1∶50) autoantibodies of the mice prolonged APD_(20), APD_(50), APD_(90) by 36.46%, 29.63% and 12.40%, respectively and enhanced L type Ca^(2+) currents by (49.67±16.01)%. CONCLUSIONS: Autoantibodies against β_1-adrenoceptors of the mice induced by hepatitis B virus result in several arrhythmias, which might be mediated by the enhancement of L type Ca^(2+) currents.