扎考必利对哇巴因诱发的成年大鼠心律失常的抑制作用

发布时间：2018-05-11 23:16

本文选题：心律失常 + 内向整流钾通道　；参考：《中国病理生理杂志》2017年08期

【摘要】：目的:观察内向整流钾通道激动剂扎考必利(zacopride)对哇巴因(ouabain)诱发的成年大鼠心律失常的影响,并探讨其电生理机制。方法:利用ouabain建立成年大鼠离体和在体心律失常模型,观察zacopride对各类心律失常的作用。应用全细胞膜片钳技术,观察zacopride对大鼠单个心室肌细胞内向整流钾电流(I_(K1))、静息膜电位(RMP)及延迟后除极(DADs)的影响。结果:浓度为1μmol/L的zacopride使ouabain诱发的离体心脏期前收缩个数、室速和室颤持续时间及发生率均显著降低(P0.05)。在麻醉大鼠,15μg/kg的zacopride使ouabain诱发的期前收缩个数、室速和室颤持续时间及发生率均显著降低(P0.05)。Ouabain使I_(K1)明显减小(P0.05),而0.1~10μmol/L zacopride可部分恢复甚至完全逆转ouabain对I_(K1)的抑制作用,其中1μmol/L为最大效应浓度。Ouabain使RMP减小(P0.05),应用zacopride(0.1~10μmol/L)后,RMP呈不同程度地增大,zacopride在1μmol/L时达最大效应浓度,使RMP增大至接近正常水平。1μmol/L的zacopride可有效抑制ouabain诱发的成年大鼠心室肌细胞DADs,使其发生率由91.67%下降至12.50%(P0.05);在灌流液中加入1μmol/L BaCl_2后,DADs再次出现。结论:内向整流钾通道激动剂zacopride对ouabain诱发的成年大鼠室性心律失常具有明显抑制作用,其机制与zacopride适度增强I_(K1)、使RMP负值增大并抑制DADs有关。
[Abstract]:Objective: To observe the effect of zacopride on the arrhythmia of adult rats induced by ouabain (ouabain), and to explore its electrophysiological mechanism. Methods: using ouabain to establish adult rats in vitro and in vivo arrhythmia model, observe the effect of zacopride on all kinds of arrhythmia. The effect of zacopride on internal rectifying potassium current (I_ (K1)), resting membrane potential (RMP) and delayed depolarization (DADs) in rat single ventricular myocytes was observed. Results: the number of ventricular tachycardia, ventricular tachycardia and ventricular fibrillation duration and incidence were significantly decreased (P0.05), and the duration and incidence of ventricular fibrillation were significantly reduced (P0.05) by zacopride with a concentration of 1 mu mol/L (P0.05). The number of ouabain induced ouabain induced contractions, ventricular tachycardia and ventricular fibrillation duration and occurrence rate decreased significantly (P0.05).Ouabain made I_ (K1) significantly decreased (P0.05), and 0.1~10 micron mol/L zacopride could partly restore and even completely reverse the inhibition effect of ouabain on ouabain, of which 1 mu was the maximum effect concentration. P decreased (P0.05). After the application of zacopride (0.1~10 mu mol/L), RMP increased in varying degrees. Zacopride reached the maximum effect concentration at 1 u mol/L. The zacopride could increase the RMP to the normal level.1 mu mol/L. After adding 1 mol/L BaCl_2, DADs appeared again. Conclusion: the introverted rectifier potassium channel agonist zacopride has a significant inhibitory effect on ouabain induced ventricular arrhythmias in adult rats. The mechanism is moderately enhanced by I_ (K1) with zacopride and increases the negative value of RMP and inhibits DADs.

【作者单位】：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;西藏民族大学机能教研室;
【基金】：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) 山西省高等学校优秀青年学术带头人支持项目
【分类号】：R541.7

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