银杏酮酯通过抑制钠、钙通道和自发性钙波防治心律失常  

GBE50 alleviates cardiac arrhythmias via inhibition of I_(Na) and I_(Ca,L) and spontaneous calcium waves

作　　者：刘备 张光永 刘爱华[1] 张志雄[1] 王星禹[1] LIU Bei;ZHANG Guang-yong;LIU Ai-hua;ZHANG Zhi-xiong;WANG Xing-yu(Dept of Physiology,Shanghai University of T.C.M,Shanghai 201203,China)

机构地区：[1]上海中医药大学基础医学院生理教研室,上海201203

出　　处：《中国药理学通报》2021年第12期1721-1726,共6页Chinese Pharmacological Bulletin

基　　金：国家自然基金资助项目(No 81202945);上海中医药大学预算内科研项目(No 18LK001,2020LK001),上海市中药专家传承工作室建设项目(2020ZYGZS-010)。

摘　　要：目的观察银杏酮酯(ginkgo biloba extract 50,GBE50)对心室肌细胞钠通道和钙通道电流的作用及缺血/再灌时自发性钙波的影响,明确其抗心律失常作用的机制。方法使用乌头碱诱导心肌细胞心律失常的模型,膜片钳技术测量和分析钠电流(I_(Na)),L型钙电流(I_(Ca,L))。激光共聚焦钙离子成像观察缺血/再灌注心室肌细胞钙波信号。结果乌头碱可导致心室肌细胞I_(Na)和I_(Ca,L)最大电流密度增加,激活曲线左移,半激活电压增加,而25 mg·L^(-1) GBE50使I_(Na)和I_(Ca,L)最大电流密度减小,激活曲线右移,半激活电压减少。缺血/再灌注使心室肌细胞自发性钙波增多,25 mg·L^(-1) GBE50可减少钙波发生。结论GBE50减弱由乌头碱增强的I_(Na)和I_(Ca,L),抑制缺血/再灌注导致自发性钙波的发生,可能是GBE50抗心律失常的机制之一。Aim To test the antiarrhythmic effect of GBE50 on aconitine-induced abnormal inward current(I_(Na) and I_(Ca,L))and spontaneous Ca^(2+) waves during ischemia reperfusion in ventricular myocytes of rats and the underlying mechanism.Methods Ventricular myocytes were isolated from SD rat hearts via enzymatic dissociation.I_(Na) and I_(Ca,L) were record by whole-cell patch clamp in voltage clamp mode.Intracellular Ca^(2+)was labelled by Fluo-4-AM,and spontaneous Ca^(2+) waves of ischemia reperfusion myocytes were detected in line-scan mode by laser confocal microscopy.Results The peak density of I_(Na) and I_(Ca,L) was raised by aconitine with the I-V curve shifting downward,while GBE50 was able to restore the increase of I_(Na) and I_(Ca,L) caused by aconitine.Ischemia-reperfusion in cardiomyocytes produced spontaneous calcium waves and GBE50 reduced spontaneous calcium waves in ischemia-reperfusion myocardial cells.Conclusion GBE50 could inhibit I_(Na) and I_(Ca,L) activation and spontaneous calcium waves,which is suggested to be one of the mechanisms of the antiarrhythmic effects of GBE50.

关 键 词：银杏酮酯 心律失常 钠通道 钙通道 钙波 乌头碱 

分 类 号：R-332[医药卫生] R284.1