植物源天然钙离子通道拮抗剂在抗心律失常药物开发中的应用研究进展  

Research progress on applying plant-derived natural calcium channel blockers in the antiarrhythmic drug development

作　　者：蒲利华 贺爽[1,2] 周正灿 朱彦[1,2] PU Li-hua;HE Shuang;ZHOU Zheng-can;ZHU Yan(State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Research and Development Center of Traditional Chinese Medicine,Tianjin International Joint Academy of Biomedicine,Tianjin 300457,China)

机构地区：[1]天津中医药大学组分中药国家重点实验室,天津301617 [2]天津国际生物医药联合研究院中药新药研发中心,天津300457

出　　处：《药学学报》2022年第10期3027-3034,I0007,共9页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划项目(2018YFC1704502);国家自然科学基金资助项目(81873037);国家科技重大专项资助项目(2018ZX01031301)。

摘　　要：心律失常是心脏活动的起源和/或传导障碍导致的心脏搏动频率和/或节律异常。心律失常疾病表现多样且病因复杂,可单独发生,也可与其他心血管疾病并发;可突然发作导致猝死,也可持续发作导致心力衰竭。在心肌细胞中,钙超载可诱导细胞凋亡,导致心律失常的发生。钙通道阻滞剂作为调节钙信号的心血管常规药物已在临床广泛使用,但其对不同心律失常并发症的疗效不尽相同,且具有潜在的治疗风险。因此,从植物和其他天然产物资源寻求针对新作用机制和靶标的钙离子信号调节剂并将其开发为安全性更高、疗效更为显著的心律失常治疗药物意义重大。本文着眼于植物源天然钙离子通道拮抗剂对心律失常模型中钙离子信号的调控作用,对近年的研究成果进展予以综述,汇总了通过调控Ca^(2+)稳态而抗心律失常的生物碱、皂苷、醌类和黄酮类化合物等多种天然药物的作用和机制,以期为今后运用天然产物钙离子通道拮抗剂防治心律失常进行的药物开发提供理论依据。Arrhythmia is the abnormal heart-beat frequency and/or rhythm caused by the origin of cardiac activity and/or conduction disorder.Arrhythmia disease has various manifestations and complex etiology,which can occur alone or complicated with other cardiovascular diseases.A sudden arrhythmic onset may lead to sudden death,whereas a sustained onset may lead to heart failure.In cardiomyocytes,calcium overload induces apoptosis and leads to arrhythmia.Calcium channel blockers have been widely used in clinic as a routine cardiovascular drug to regulate calcium signal,but their efficacy on different arrhythmia complications vary,and they also have potential therapeutic risks.Therefore,it is of great significance to seek calcium signal modulators targeting new mechanisms from plants and other natural product resources and develop them into anti-arrhythmia drugs with higher safety and better curative effect.This review focuses on the calcium signal regulatory effects of plant-derived natural calcium channel antagonists in arrhythmia models,highlights the research progress in recent years,and summarizes the effects and mechanisms of various natural drugs such as alkaloids,saponins,quinones and flavonoids,which regulate Ca^(2+)homeostasis,to provide a theoretical basis for the drug development of natural calcium channel antagonists to prevent and treat arrhythmia in the future.

关 键 词：心律失常 钙离子通道拮抗剂 天然药物 生物活性成分 钙信号 

分 类 号：R965[医药卫生—药理学]