包公藤甲素衍生物(S)-OTS·HCl的心脏电生理效应  

Cardiac electrophysiological effect of(S)-OTS·HCl, a derivative of Baogongteng A

作　　者：王红卫[1] 张颖[2] 李慈珍[3] 刘远谋[3] 杨智昉[1] WANG Hong-wei;ZHANG Ying;LI Ci-zhen;LIU Yuan-mou;YANG Zhi-fang(Department of Physiology, Shanghai University of Medicine and Health Science, Shanghai 201318, China;Experimental Center, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China;Department of Physiology, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China)

机构地区：[1]上海健康医学院基础医学院生理教研室,上海201318 [2]上海交通大学基础医学院实验中心,上海200025 [3]上海交通大学基础医学院生理教研室,上海200025

出　　处：《上海交通大学学报（医学版）》2017年第2期177-183,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海科学技术委员会重点资助项目(06JC14045);上海教育委员会科研创新项目(13yz150);上海健康医学院附属卫生学校课题(FA1-3903-16-117067)~~

摘　　要：目的·研究(S)-OTS·HCl对心脏生物电活动的影响。方法·运用细胞内生物电记录、心电图及Langendorff心脏灌流技术,在离体和在体情况下研究(S)-OTS·HCl对豚鼠和家兔心脏的作用。结果·(S)-OTS·HCl可与M_2型胆碱能受体结合,并在动物整体心电图记录中剂量依赖性地延长RR间期。(S)-OTS·HCl对心室肌的静息电位(RP)、动作电位幅值(APA)和动作电位最大上升速率(V_(max))没有影响,但(S)-OTS·HCl(1×10^(-5) mol/L)可显著缩短动作电位时程APD_(50)和APD_(90)分别至91.6%和90.9%。当(S)-OTS·HCl(1×10^(-7) mol/L)灌流家兔窦房结标本时,可使4期自动除极速率缩短至13.7%,也可有效抑制钙通道,并使窦房结自律性动作电位的APA和V_(max)减小。离体心肌收缩力亦随(S)-OTS·HCl的剂量增加而降低。结论·(S)-OTS·HCl是一个作用较强的胆碱能受体激动剂,能与心肌M_2受体结合,产生负性变时、变力和变传导效应。To study the electrophysiological effect of (S)-OTS·HCl on the heart. Methods · The conventional intracellular recording,electrocardiograph (ECG) and Langendorff cardiac perfusion technique were employed to investigate the effect of (S)-OTS·HCl on in-vivo and in-vitro hearts of guinea pigs and rabbits. Results · (S)-OTS·HCl could bind to M2 muscarinic receptors and dose-dependently prolong the RR intervals significantly in vivo.It had no effect on resting potential (RP), action potential amplitude (APA), and maximum upstroke velocity of phase 0 (Vmax) of ventricular myocytes. Instead,1×10-5 mol/L (S)-OTS·HCl could shorten the action potential duration at 50 percent repolarization (APD50) and APD90 to 91.6% and 90.9%, respectively.And the spontaneous depolarization rate of phase 4 (SDR) of sinus nodes was reduced to its 13.7% when rabbit sinus nodes were exposed to 1×10-7 mol/L(S)-OTS·HCl. (S)-OTS·HCl could inhibit Ca2+channel effectively. It decreased APA and Vmax of sinus nodes and attenuated the cardiac contractility in vitro.Conclusion · (S)-OTS·HCl is a potent cholinergic agonist and has negative chronotropic, dromotropic, and inotropic effects on hearts via binding to M2muscarinic receptors.

关 键 词：(S)-OTS·HCl 胆碱能受体激动剂 动作电位 心电图 

分 类 号：R96[医药卫生—药理学]