中国病理生理杂志2017，Vol.33Issue(8)：1371-1378,8.DOI:10.3969/j.issn.1000-4718.2017.08.005
扎考必利对哇巴因诱发的成年大鼠心律失常的抑制作用
Inhibitory effect of zacopride on ouabain-induced arrhythmias in adult rats
摘要
Abstract
AIM: To investigate the effect of zacopride, an inward rectifier potassium channel agonist, on ouabain-induced arrhythmias in adult rats, and to explore the underlying electrophysiological mechanism.METHODS: Using ouabain to establish in vitro and in vivo arrhythmic rat models, the effects of zacopride on ouabain-induced arrhythmias were observed.The technique of whole-cell patch clamp was used to observe the effects of zacopride on inward rectifier potassium current (IK1), resting membrane potential (RMP) and delayed afterdepolarizations (DADs) in single rat ventricular myocyte.RESULTS: Zacopride at 1 μmol/L significantly reduced total number of premature ventricular beats, and the duration and incidence of ventricular tachycardia and ventricular fibrillation induced by ouabain in rat hearts in vitro (P<0.05).In anesthetized rats, zacopride at 15 μg/kg significantly reduced total number of premature ventricular beats, and the duration and incidence of ventricular tachycardia and ventricular fibrillation induced by ouabain (P<0.05).IK1 was significantly inhibited by ouabain (P<0.05), which was partially and even completely reversed by zacopride at 0.1~10 μmol/L.RMP value was significantly reduced by ouabain (P<0.05), and then increased to different levels after treatment with zacopride (0.1~10 μmol/L).Zacopride at 1 μmol/L showed its maximal effect and RMP was restored to normal level.Moreover, zacopride at 1 μmol/L markedly suppressed ouabain-induced DADs in single rat ventricular myocyte.The incidence of DADs decreased from 91.67% to 12.50% after zacopride was applied (P<0.05), and this effect was abolished by 1 μmol/L BaCl2.CONCLUSION: Inward rectifier potassium channel agonist zacopride significantly inhibits ouabain-induced ventricular arrhythmias in adult rats.The mechanism is related to increased RMP level and inhibition of DADs by activation of IK1 channel.关键词
心律失常/内向整流钾通道/静息膜电位/延迟后除极/全细胞膜片钳Key words
Arrhythmia/Inward rectifier potassium channel/Resting membrane potential/Delayed afterdepolarization/Whole-cell patch clamp分类
医药卫生引用本文复制引用
王晓露,杨明珠,薛晓艳,张堉琪,陈依春,封启龙,吴博威..扎考必利对哇巴因诱发的成年大鼠心律失常的抑制作用[J].中国病理生理杂志,2017,33(8):1371-1378,8.基金项目
高校"131"领军人才工程优秀中青年拔尖创新人才 （）
山西省重点实验室建设项目(No.2015012003-08) （No.2015012003-08）
山西省高等学校优秀青年学术带头人支持项目 （）
