昼夜节律参与急性心肌梗死发生的机制及相关治疗进展

Role of circadian rhythm in initiation of acute myocardial infarct and progress of targeted therapeutic strategies

流行病学数据显示急性心肌梗死(AMI)发病高峰集中在上午6:00-12:00之间,夜间20:00又有一次高峰。其发生可看做是应激因素(外因)与节律因素(内因)间相互作用的结果,但发生机制尚未完全阐明。现今认为此现象与清晨前后交感神经系统活性迅速增强,儿茶酚胺类血管活性物质释放增多以及肾素血管紧张素系统(RAS)激活有关。目前研究证实,在哺乳类动物中生物时钟运作至少有8个核心生物时钟基因参与:Period I(Per 1)、Period 2(Per 2)、Period 3(Per3)、Cryptochrome 1(Cry 1)、Cryptochrome 2(Cry 2)、CLOOK、BMAL 1和Casein kinase Iε。随着AMI昼夜节律性研究的深入,时间治疗学应运而生,可根据不同患者的病理生理状态下的昼夜节律性,结合时间治疗学制定出个体化的治疗措施。本文就急性心肌梗死与血压、凝血节律性的关系、涉及机制及时间治疗学作一综述。

Period of circadian rhythms is around 24 hours,which is generated and maintained by mutual positive and negative feedback of the core circadian clock genes,invob ing with the interaction among central nervous system,peripheral nervous system,endocrinal system and outside environment.Disruption of circadian rhythms often occur when bodies＇ sleep or diet process don＇t keep with core circadian system or day-night cycle,particularly among the shiftvvorking people.Data from epidemiologic Studies uncovered that acute cardiovascular events such as angina pectoris,myocardial infarction,sudden death and ventricular arrhythmia often occurred in the morning.Furthermore blood pressure,coagulation system and etc el al also showed similar phenomena.Recently chronotherapy strategies have been attracting more and more attention for potential resynchronization of the internal circadian system and decrease of such cardiovascular risk caused by dys-synchronization of circadian system.Based on the above,the complex relationships between AMI occurrence and circadian rhythm of blood pressure and coagulation system,relative mechanism and process of chronotherapy strategics are summarized in this article.