Arctigenin, a Potential Anti-Arrhythmic Agent, Inhibits Aconitine-Induced Arrhythmia by Regulating Multi-Ion Channels
Arctigenin, a Potential Anti-Arrhythmic Agent, Inhibits Aconitine-Induced Arrhythmia by Regulating Multi-Ion Channels
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牛蒡甙元是一种潜在的抗心律失常药，通过调节多离子通道抑制乌头碱诱发的心律失常
DOI：
10.1159/000354532
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发表时间：
2013
影响因子：
--
通讯作者：
Luo Guo'an
中科院分区：
文献类型：
--
作者：
Zhao Zhenying;Yin Yongqiang;Wu Hong;Jiang Min;Lou Jianshi;Bai Gang;Luo Guo'an
背景/目的：牛蒡甙元具有生物活性，但其在细胞和离子通道水平的潜在机制尚不完全清楚。因此，本研究旨在确定牛蒡子苷元的体内抗心律失常作用及其细胞靶点和机制。方法：通过连续输注乌头碱建立大鼠心律失常模型，记录室性早搏、室性心动过速和死亡的发生次数。采用膜片钳记录技术对正常大鼠心肌细胞和乌头碱诱发心律失常的心肌细胞进行动作电位持续时间（APD）、钠电流（INa）、L型钙电流（ICa，L）和瞬时外向钾电流（Ito）的测量和分析。结果：牛蒡甙元显着延迟乌头碱诱导的大鼠模型中心律失常的发生。 100 µM 牛蒡甙元缩短了 50% 和 90% 复极（APD50 和 APD90）；牛蒡甙元剂量还抑制1μM乌头碱引起的APD50和APD90的延长。牛蒡甙元抑制 INa 和 ICa,L，并通过加速激活过程和延迟失活过程来减弱乌头碱增加的 INa 和 ICa,L。牛蒡甙元通过促进激活过程和延迟失活过程来增强Ito，并恢复乌头碱引起的降低的Ito。结论：牛蒡甙元在体内和体外均具有抗心律失常作用。在电生理学背景下，INa、ICa、L 和 Ito 可能是牛蒡甙元的多个靶点，从而发挥其抗心律失常作用。
Background/Aims: Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. Methods: A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (INa), L-type calcium current (ICa, L) and transient outward potassium current (Ito) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Results: Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited INa and ICa,L and attenuated the aconitine-increased INa and ICa,L by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Conclusions: Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, INa, ICa, L, and Ito may be multiple targets of arctigenin, leading to its antiarrhythmic effect.