苄基异喹啉类生物碱抗心律失常离子机制研究进展

Research Progress on Antiarrhythmic Ion Mechanism of Benzylisoquinoline Alkaloids

苄基异喹啉类生物碱(Benzylisoquinoline alkaloids, BIAs)属于异喹啉类生物碱中的一类,根据其化学结构特点可分为小檗碱(Berberine, BBR)和原小檗碱类、阿朴菲类、苄基四氢异喹啉类、普罗托品类、双苄基异喹啉类等。此类生物碱来源中药及中药组方在治疗心悸、怔忡、厥证、胸痹等心血管相关疾病方面也有着丰富的临床用药经验,现代研究表明苄基异喹啉类生物碱具有较强的抗心律失常活性,从中药中开发抗心律失常单体活性成分,毒性、不良反应更清楚,开发成本更低。基于心律失常发病机制复杂的特点,通过多途径,多靶点作用的抗心律失常药物具有更高的安全性和有效性,现在临床使用的抗心律失常药物大多属于单离子通道阻滞剂,具有致心律失常风险,而苄基异喹啉类生物碱可通过影响Na+、K+、Ca2+多条离子通道、抗炎及氧化应激途径达到治疗多种心律失常的目的,极具开发前景。通过查阅、整理近40年的国内外文献,结合中医药理论对苄基异喹啉类生物碱的抗心律失常离子机制进行总结,可为开发安全高效的抗心律失常药物和治疗手段提供参考。

Benzylisoquinoline alkaloids(BIAs)belong to a class of isoquinoline alkaloids.According to the chemical structure,they can be divided into berberine and protoberberines,apophines,benzyltetrahydroisoquinolines,protopines and bisbenzylisoquinolines,etc.Such alkaloid-derived traditional Chinese medicines and traditional Chinese medicine prescriptions also have rich clinical experience in the treatment of cardiovascular-related diseases such as palpitations,severe palpitations,syncopy,chest arthralgia,etc.Modern research shows that benzylisoquinoline alkaloids have strong anti-arrhythmic effect.The development of anti-arrhythmic monomer active ingredients from traditional Chinese medicine as well as the toxicity and side effects are clearer,and the development cost is lower.Based on the complex pathogenesis of arrhythmia,antiarrhythmic drugs that act through multiple pathways and multiple targets have higher safety and efficacy.Most of the antiarrhythmic drugs currently in clinical use belong to single ion channel blockers,which have the risk of proarrhythmia.However,benzylisoquinoline alkaloids can achieve the purpose of treating various arrhythmias by affecting Na+,K+and Ca2+ion channels,anti-inflammatory and oxidative stress pathways,and have great development prospects.This article summarized the antiarrhythmic ionic mechanism of benzylisoquinoline alkaloids by reviewing and collating domestic and foreign literatures for nearly 40 years and combining with the theory of traditional Chinese medicine,which can provide reference for the development of safe and efficient antiarrhythmic drugs and treatment methods.