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心律失常发病机制研究进展

ISSN号：1674-0440
期刊名称：《国际药学研究杂志》
时间：0
分类：R331.38[医药卫生—人体生理学;医药卫生—基础医学] R541.7[医药卫生—心血管疾病;医药卫生—临床医学;医药卫生—内科学]
作者机构：[1]哈尔滨医科大学药学院药理学教研室,省部共建生物医药国家重点实验室培育基地,黑龙江哈尔滨150081
相关基金：国家重大基础研究发展计划“973 计划”项目（2007CB512000）; 国家自然科学基金重点项目（30430780）; 国家自然科学基金面上项目（30672644）; 国家自然科学基金中加国际合作项目（30711120580）

关键词：心律失常, 离子通道, 小分子RNA, M3受体, 心房颤动, 缝隙连接蛋白, 心肌梗死, AT1受体, 溶血磷脂酰胆碱类, arrhythmia, ion channels, microRNA, M3 receptor, atrial fibrillation, gap junction protein, myocardial infarction, AT1 receptor, lysophosphatidylcholines

中文摘要：

心律失常是心血管疾病常见的临床表现形式,尤其是室性心动过速、心室颤动等恶性心律失常,不但加重原有心脏疾病,还可诱发心源性猝死。目前抗心律失常药物的疗效并不十分理想,总有效率只有30%～60%。人们对心律失常作用机制的认识仍有限,因此,揭示心律失常发生的深层机制,寻找新的作用靶点是抗心律失常研究领域的重点、难点。近年人们发现心房特异性钾离子通道电流IKur、IKAch等参与了心房颤动,这使心房颤动治疗的研究向前推进一步。钙渗漏、缝隙连接蛋白及钙通道自身抗体在心律失常发生中发挥重要作用。这些发现为开发更有效的抗心律失常药物提供了理论基础。近年研究发现,一类调控基因的小分子RNA（microRNA,miRNA）在心血管疾病的发生、发展中起重要作用,特别是对心律失常及其引起的猝死起关键作用。miR-1、miR-133、miR-590等对心肌缺血、心肌梗死伴随的心律失常表现出明显调控作用。miRNA的生物学特性是同时对多个靶点具有调控作用,这使其具有成为理想抗心律失常靶点的潜力,为心律失常及猝死的防治带来希望。

英文摘要：

Arrhythmia is a common complication of cardiovascular diseases and a risk factor for human health.Especially,ventricular tachycardia and ventricular fibrillation may not only exacerbate original heart diseases,but also cause cardiac sudden death which has been an important death reason in China.However,anti-arrhythmic drugs nowadays cannot effectively treat these arrhythmias,with an efficiency of only 30%-60% ,which indicates that our knowledge about arrhythmias is limited.Hence,to explore the potential mechanism,look for novel targets,and develop drugs with multiple-channel action are the focus of the research direction.Recent studies displayed that the atrial-specific potassium channels such as IKur and IKAch were involved in atrial fibrillation,which provided a prospective target for atrial fibrillation treatment.Calcium leak,gap junction protein and autoantibody against ICaL channel were shown to participate in arrhythmogenesis.These findings provided a theoretical basis for the development of more effective anti-arrhythmic drugs.Remarkably,as a kind of important RNA regulating gene expression,microRNA（miRNA） was shown to possess anti-arrhythmic activities which may prevent cardiac sudden death.miR-1,miR-133 and miR-590 regulated the arrhythmia in various types of animal models.Because of the multiple-gene regulation actions of miRNA,it has the potential to be developed as novel anti-arrhythmic target.

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