传统抗心律失常药物及苦参碱对家兔心室肌细胞快速延迟整流钾电流作用的比较

Comparison of the effect of the antiarrhythmic drugs and matrine on rapidly delayed outward rectifying potassium channel in rat ventricular myocytes

目的比较传统的抗心律失常药物和苦参碱对心肌细胞快速延迟整流钾电流(IKr)的作用,以及其诱发QT间期延长和致心律失常作用发生的危险性。方法采用酶解法急性分离单个家兔心室肌细胞,全细胞膜片钳技术观察并比较奎尼丁、普萘洛尔、胺碘酮及苦参碱等药物对心肌细胞IKr的作用。结果胺碘酮(0.1、1和10μM)及苦参碱(1、10和100μM)剂量依赖性抑制家兔心室肌细胞IKr,而苦参碱的抑制作用明显弱于胺碘酮;几种传统的抗心律失常药物中,在相同药物浓度下(1μM),奎尼丁和胺碘酮均表现为明显的IKr电流抑制作用,而普萘洛尔对IKr电流的抑制作用明显减轻(n=12,P<0.05)。结论中药苦参碱及β受体阻断药普萘洛尔对IKr电流的抑制作用较奎尼丁和胺碘酮为弱,其临床应用不易诱发QT间期延长和心律失常。

[Objective]To observe the effect of the conventional antiarrhythmic drugs and carpidine on rapidly delayed outward rectifying potassium channel（IKr） in rat ventricular myocytes and compare the risk of inducing Long QT （LQT） and arhythmia.[Methods]Ventricular myocytes in rat were isolated with enzymatic technique and the effect of these substances on IKr was observed with whole cell patch clamp technique.[Results]Amiodaron （0.1, 1, 10 μM） and matrine inhibit the IKr in rat ventricular myocyte dose dependently and the depressant effect of matrine was weaker than amiodaron. The depressant effects of quinidine and amiodarone were evident and the effect of propranolol decreased weaker apparently at the same drug concentration （1 μM）.[Conclusion]The depressant effects on IKr of the traditional Chinese drug matrine and propranolol are weak and the risk of inducing LQT is tiny.