心律失常与活性氧物质和内质网应激及线粒体功能障碍的关系
本公众号每天分享一篇最新一期Anesthesia & Analgesia等SCI杂志的摘要翻译，敬请关注并提出宝贵意见
Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis
背景与目的：心律失常是一个全球性的难题，它与脑血管事件、心肌梗死和心源性猝死的发生息息相关。目前越来越多的研究表明：高血压和糖尿病等病理条件下，活性氧物质（ROS）增高所致的氧化应激反应最终导致了心律失常的发生。
1
方法：本篇文章通过文献综述的形式探究了ROS对心肌离子通道功能、心肌重构及心律失常的影响。
结果：心衰增强内质网应激能增加ROS的产生。糖尿病和高血压患者线粒体中增高的ROS能在线粒体中形成一个正反馈循环，即ROS诱导ROS的释放。同时，线粒体中增高的ROS还能激活线粒体内膜的阴离子通道最终导致线粒体膜发生了去极化。此外，内质网和线粒体的功能障碍还可以激活下游的信号传导通路最终导致与动作电位（AP）形成相关的离子通道的功能和表达改变。血管和心肌内皮细胞的功能障碍能改变旁分泌信号的传导并最终影响了相邻心肌细胞间电生理活动。上述的所有改变所造成的AP复极化和传导的障碍最终可以增加触发活动和折返发生的可能。
结论：ROS与心律失常的发生息息相关。以减少上游事件为治疗的策略包括减少环境应激和使用以细胞器特异性蛋白或离子通道为治疗靶点的药物。这些治疗策略可以减少氧化应激从而预防糖尿病病人和高血压病人以及心衰病人心律失常的发生。
Tse G, Yan B P, Chan Y W F, et al. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction:The Link with Cardiac Arrhythmogenesis.[J]. Frontiers in physiology, 2016,7:313.
BACKGROUND: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS), which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis.
METHODS:A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function,remodeling and arrhythmogenesis.
RESULTS:Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS,which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation of mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signaling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP). Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signaling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry.
CONCLUSIONS:ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension, and heart failure.
麻醉学文献进展分享
联系我们