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用生物学方法重建心脏起搏点的研究进展

萧永福, Sigg D C

美敦力公司心脏节律和疾病管理.明尼苏达州 55432

摘要

正常人的心脏节律源于右心房的天然起搏点(pacemaker)-----窦房结。窦房结的功能异常或者房室传导阻滞会导致心率异常(如心律缓慢)。治疗严重的心动过缓需要植入在技术上已经相当成熟的电子起搏器,但这种治疗存在一些缺陷和不足。近年来,在动物实验模型中应用基因或细胞来重建心脏的生物起搏点已经取得了进展。超极化活化环核苷酸门控(hyperpolarization--activated cyclic--nucleotide--modulated,HCN)通道(起搏通道)通过超极化活化的阳离子电流(hyperpolarization--activated cation current,{sl I}_(f))调制心脏的自律性。利用病毒载体或转染HCN基因的细胞将HCN基因导入动物心脏内可重建生物起搏点。也有导入其它基因或植入自律细胞来探索心脏起搏点的重建。该文总结了重建心脏生物起搏点的一些研究进展。一旦稳定性和寿命等关键问题得到相应解决,遗传工程改造的生物起搏点可用于治疗严重的心动过缓。

关键词： 窦房结; 生物起搏点; 基因; 干细胞; 超极化活化环核苷酸门控通道

Biological approaches to generating cardiac biopacemaker for bradycardia

Xiao Yongfu, Sigg D C

Cardiac Rhythm Disease Management, Medtronic Inc., Minneapolis,MN 55432

Abstract

Normal rhythm in a healthy human heart originates from the natural biological pacemaker, the sinoatrial (SA) node which locates in the right atrium. SA node dysfunction or atrial-ventricular (AV) conduction block causes improper heart rate (bradycardia).Such dysfunction, if severe enough, is currently treated by implanting an electronic pacemaker which has been well established technically, but there are some limitations and inadequacies. Recently, progress in developing engineered cardiac biopacemakers with use of genes or cells has been made in experimental animal models. The hyperpolarization-activated cyclic-nucleotide-modulated(HCN) channel (pacemaker channel) modulates cardiac automaticity via the hyperpolarization-activated cation current (I_(f)). HCN genes have been delivered to animal myocardium via viral vectors or HCN-transferred cells for recreating biological pacemakers. Approaches with non-HCN genes or transplantation of beating cells are also novel and have been investigated for generating cardiac biopacers. This article summarizes the progresses in research on recreation of cardiac biopacemakers. Genetically engineered biological pacemaker holds great promise to potentially cure severe bradycardia if critical issues, such as their stability and longevity, are properly solved.

Key words: Sinoatrial node;biological pacemaker;Gene;stem cell;hyperpolarization-activated cyclic-nucleotide-modulated channel

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引用本文：

萧永福, Sigg D C. 用生物学方法重建心脏起搏点的研究进展[J]. 生理学报 2007; 59 (5): 562-570.

Xiao Yongfu, Sigg D C. Biological approaches to generating cardiac biopacemaker for bradycardia. Acta Physiol Sin 2007; 59 (5): 562-570 (in Chinese with English abstract).