上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

包公藤甲素衍生物(S)-OTS·HCl的心脏电生理效应

王红卫 1，张颖 2，李慈珍 3，刘远谋 3，杨智昉 1   

  1. 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
  • 出版日期:2017-02-28 发布日期:2017-02-28
  • 通讯作者: 杨智昉，电子信箱：yangzhifang@189.cn。
  • 作者简介:王红卫（1967—），男，副教授，硕士；电子信箱：jywanghw@shsmu.edu.cn。
  • 基金资助:

    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（FA1-390316-117067）

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

WANG Hong-wei1, ZHANG Ying2, LI Ci-zhen3, LIU Yuan-mou3, YANG Zhi-fang1   

  1. 1. Department of Physiology, Shanghai University of Medicine and Health Science, Shanghai 201318, China; 2. Experimental Center, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China; 3. Department of Physiology, Basic Medicine Faculty of Shanghai Jiao Tong University,Shanghai 200025, China
  • Online:2017-02-28 Published:2017-02-28
  • Supported by:

    Key Project of Science and Technology Commission of Shanghai Municipality, 06JC14045; Scientific Research Innovation Project of Shanghai Education
    Committee, 13yz150; Subject of Health School Affiliated to Shanghai University of Medicine and Health Sciences, FA1-3903-16-117067

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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M2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（Vmax）没有影响，但(S)-OTS · HCl（1×10-5 mol/L）可显著缩短动作电位时程APD50和APD90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Vmax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M2受体结合，产生负性变时、变力和变传导效应。

关键词: (S)-OTS ·, HCl；胆碱能受体激动剂；动作电位；心电图

Abstract:

Objective · 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 M2 muscarinic receptors.

Key words: (S)-OTS·HCl, cholinergic agonist, action potential, electrocardiograph