钠-钙交换体单克隆抗体NCX-2D2对异丙肾上腺素诱发成年大鼠心律失常的抑制作用  

Inhibitory effect of monoclonal antibody NCX-2D2 on isoproterenol-induced arrhythmias in adult rat hearts

作　　者：薛晓艳 王苗苗 王晓露 杨明珠 吴博威[1] 封启龙[1] XUE Xiao-yan;WANG Miao-miao;WANG Xiao-lu;YANG Ming-zhu;WU Bo-wei;FENG Qi-long(Dept of Physiology,Shanxi Medical University,Key Lab of Cellular Physiology of Shanxi Province and Ministry of Education,Taiyuan 030001,China;Dept of Functioning,Jinci College of Shanxi Medical University, Taiyuan 030025,China;Dept of Medicine,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]山西医科大学生理学系,细胞生理学省部共建教育部重点实验室,山西太原030001 [2]山西医科大学晋祠学院机能教研室,山西太原030025 [3]中山大学中山医学院,广东广州510080

出　　处：《中国药理学通报》2018年第9期1308-1314,共7页Chinese Pharmacological Bulletin

基　　金：山西省归国留学人员基金资助项目(No2017-055);山西省重点实验室建设项目(No2015012003-08);山西省高等学校优秀青年学术带头人支持项目;山西省“1331工程”重点学科建设计划经费资助

摘　　要：目的观察钠-钙交换体单克隆抗体NCX-2D2对异丙肾上腺素(isoproterenol,ISO)诱发大鼠心律失常的影响,并探讨其电生理机制。方法利用ISO建立大鼠离体和在体心律失常模型,观察NCX-2D2抗体对心律失常的影响;通过全细胞膜片钳技术,观察NCX-2D2抗体对大鼠心室肌细胞I_(Na/Ca)、I_(Ca-L)和DADs的作用。结果 10 mg·L^(-1) 2D2抗体可明显抑制ISO诱发大鼠离体心脏心律失常的发生(P<0.01);80μg·kg^(-1) 2D2抗体可明显抑制ISO诱发麻醉大鼠心律失常的发生(P<0.01);5 mg·L^(-1) 2D2抗体可部分抑制ISO对大鼠心室肌细胞I_(Na/Ca)的增大作用(P<0.01),以及对I_(Ca-L)的增大效应(P<0.01),并可有效抑制ISO诱发大鼠心室肌细胞DADs的发生(P<0.05)。结论钠-钙交换体单克隆抗体NCX-2D2可明显抑制异丙肾上腺素诱发的大鼠室性心律失常,其抗心律失常机制与抑制心肌细胞钠-钙交换体和L-型钙通道,从而减轻钙超载和抑制延迟后除极有关。To investigate the effects of monoclonal antibody NCX-2D2 on isoproterenol-induced arrhythmias in rat hearts,and to explore the electrophysiological mechanism.Methods Using isoproterenol to establish in vitro and in vivo arrhythmic rat models to observe the effect of NCX-2D2 antibody on ventricular arrhythmias in rats.The whole-cell patch clamp technique was used to investigate the effects of NCX-2D2 antibody on I Na/Ca,I Ca-L at voltage-clamp mode and on DADs at current-clamp mode in single rat ventricular myocytes.Results 10 mg·L^-1 NCX-2D2 antibody significantly inhibited cardiac arrhythmias induced by ISO in vitro(P<0.01).80μg·kg-1 NCX-2D2 antibody markedly inhibit the occurrence of arrhythmias in ISO-induced anesthetized rats in vivo(P<0.01).5 mg·L^-1 NCX-2D2 antibody partially inhibited the increase of I Na/Ca(P<0.01)and the increase of I Ca-L(P<0.01),and could effectively inhibit ISO-induced DADs in rat ventricular myocytes(P<0.05).Conclusions The sodium-calcium exchanger monoclonal antibody NCX-2D2 significantly inhibits isoproterenol-induced ventricular arrhythmias in rats.The mechanism against ventricular arrhythmias is mainly due to its inhibition of cardiomyocyte sodium-calcium exchanger and L-type calcium channel and marked suppression of DADs in rat ventricular myocytes.

关 键 词：钠-钙交换体 L-型钙通道 心律失常 单克隆抗体 全细胞膜片钳技术 延迟后除极 

分 类 号：R-332[医药卫生] R322.11