心律失常,离子通道病及新药发现  

Cardiac arrhythmias,ion channelopathy and new drug discovery

作　　者：戴德哉[1] 

机构地区：[1]中国药科大学药理研究室

出　　处：《中国临床药理学与治疗学》2006年第9期961-965,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金重点课题(№30230170);面上课题(№30572193);江苏省自然科学基金(№BK2002120)

摘　　要：严重致死性心律失常的发生,均由于心肌肌膜上或肌浆网上的离子通道病变。抗心律失常药的研究不成功,防治致死性室性快速性心律失常的大型临床试验(CAST,及SWORD)失败,是由于对心肌离子通道病的认识不够。膜上hERG、MINK及SCN5A遗传基因突变使功能减低形成长QT征(LQTS),或增强功能突变(hERG,KvLQT1)形成短QT征(SQTS),或肌浆网中hRyR2突变出现CPVT,均有致死性心律失常的危险。甲状腺素致心肌肥大的心肌病具有上述基因突变的一些相似性,如APD长短不均特征,为研究心律失常机制及抗心律失常新药很好的病理模型。研制中的多通道阻断剂CPU86017及内皮素受体拮抗剂CPU0213,抗心律失常药效和纠正离子通道的作用明显,前景良好。Occurrence of severe life-threatening arrhythmias is based on ion channelopathies in the sarcolemma or sarcoplasmic reticulum of myocardium. It has not been successful in research and development of antiarrhythmic agents which failed to suppress life-threatening tachyarrhythmias in the two famous clinical trials （CAST ＆ SWORD）, attributed to lack of understanding of the channelopathy in myocardium. Patients with the LQTS （Long QT syndrome） caused by mutations in the hERG, KvLQT1 and SCN5A or the SQTS （short QT syndrome） by gain-of-function mutations in hERG and KvLQT1 or CPVT caused by mutation of RyR2 gene in sarcoplasmic reticulum, are at risk to develop life-threatening arrhythmias. Cardiomyopathy induced by L-thyroxin medication shares some resemblance with the above gene mutations and manifests varied length of APD. It provides an ideal animal model to investigate the mechanism underlying cardiac arrhythmias and evaluate activity of antiarrhythmic agents. CPU86017, an agent to block multiple ion channels, and CPU0213, a novel endothelin receptor antagonist, are under investigated and possess a promising effect to suppress cardiac arrhythmias by correcting the channelopathy in myocardium.

关 键 词：心律失常 抗心律失常药 离子通道 离子通道病 

分 类 号：R965.2[医药卫生—药理学] R541.7[医药卫生—药学]