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苦参碱、小檗胺与胺碘酮、RP58866抗心律失常作用的比较 被引量:35

Comparison of the anti-arrhythmic effects of matrine and berbamine with amiodarone and RP58866
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摘要 目的 阐明苦参碱和小檗胺抗心律失常作用弱于胺碘酮和RP58866的分子机制。方法 采用冠脉结扎、电刺激和乌头碱诱导的心律失常模型观察药物的抗心律失常作用,采用全细胞膜片钳技术测定单个心室肌细胞的Ikl,Ikr,Iks和Ito。结果 苦参碱和小檗胺对冠脉结扎、乌头碱诱发的大鼠心律失常有明显对抗作用,对家兔电刺激致颤阈(VFT)有明显提高作用,但与胺碘酮和RP58866相比,抗心律失常作用明显低于前者。电生理结果显示:苦参碱和小檗胺对家兔Ikl,Ikr,Iks和犬Ito有抑制作用,但较胺碘酮和RP58866作用弱。结论 苦参碱和小檗胺的抗心律失常作用及对Ikl,Ikr,Iks和Ito的抑制作用弱于胺碘酮和RP58866。 Aim To clarify mechanisms that the antiarrhythmic effects of matrine and berbamine are weaker than those of amiodarone and RP58866. Methods Experimental arrhythmic models were induced by aconitine, coronary artery ligation and electric stimulation in rats and rabbits. Whole-cell patch-clamp techniques were used to record IK1 , IKr, IKs and Ito. Results Matrine and berbamine significantly increased the dose of aconitine for induction of ventricular premature and ventricular tachycardia in rats, decreased the number of arrhythmias induced by coronary artery ligation in rats and increased ventricular fibrillation threshold (VFT) induced by electric stimulation in rabbits, but the anti-arrhythmic potency of matrine and berbamine was lower than that of amiodarone and RP58866. The inhibitory actions of matrine and berbamine on IK1 , IKr, IKs, Ito were lower than those of amiodarone and RP58866. The IC50 of matrine for IK1 , IKr, IKs, Ito were (46±3) , (32. 9±1.2) , (37±8) and (7. 6±0. 5) mol·L-1, respectively. The IC50 of amiodarone for IK1, IKr, IKs, Ito were (21±5) , (3. 7±0. 7) , (5. 9±0. 9) and (5. 9±0. 6) mol·L , respectively. Conclusion The inhibitory actions of matrine and berbamine on IKI , IKr, IKs, Ito were lower than those of amiodarone and RP58866, which might be the reason that the antiarrhythmic effects of matrine and berbamine were weaker than those of amiodarone and RP58866.
出处 《药学学报》 CAS CSCD 北大核心 2004年第9期691-694,共4页 Acta Pharmaceutica Sinica
基金 国家自然科学基金资助项目(39870922 30271599)
关键词 苦参碱 胺碘酮 小檗胺 RP58866 钾通道 matrine amiodarone berbamine RP58866 potassium channel
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  • 1杨宝峰 见:苏定冯 缪朝玉 王永铭主编.抗心律失常中药存在问题的探讨[A].见:苏定冯,缪朝玉, 王永铭主编.药理学进展[C].北京:人民卫生出版社,2001.126~30.

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