阻塞性睡眠呼吸暂停患者短睡与高血压的表观遗传学机制

Obstructive sleep apnea (OSA) and short sleep duration are both associated with increased risk of hypertenison. The increases of sympathetic activity may be the pathophysiological pathway for the hypertension in individuals with OSA and/or short sleep duration, whereas the sympathetic activity is regulated by genetic and environmental factors. We speculate that, 1) The patients with OSA and short sleep duration have increased 24 hours ambulatory blood pressure and sympathetic activity compared with those with OSA and normal sleep duration; 2) sympathetic activity and hypertension are associated with DNA methylation altered in sympathetic nervous system (SNS) related genes (i.e., ADRB1、ADRB2 and LPAR1) in OSA patients; 3) the efficacy of prolonged sleep duration combined with CPAP therapy is better comparing with CPAP therapy alone for OSA with short sleep duration. In our proposal, through the manners of cross-sectional and follow up therapy studies, and utilizing epigenetic measures, we plan to explore underlying epigenetic mechanisms on the mediating role of SNS in hypertension among OSA patients, and thus to provide the clues for novel preventive and therapeutic approaches for hypertension in OSA patients.

阻塞性睡眠呼吸暂停（OSA）及短睡均是高血压患病的独立风险因素，交感神经系统活性升高可能是OSA及短睡人群高血压发病风险升高的病理生理学机制；同时交感神经系统活性受到遗传及环境因素的调节。我们推测：1）睡眠时间缩短的OSA患者24小时血压水平及交感神经系统活性高于睡眠时间正常的OSA患者；2）交感神经系统基因（例如：ADRB1、ADRB2和LPAR1）的DNA甲基化水平与交感神经系统活性相关，是OSA高血压发病的表观遗传学机制；3）延长睡眠时间合并持续气道正压通气（Continuous Positive Airway Pressure，CPAP）治疗与单纯使用CPAP治疗相比，对睡眠时间缩短的OSA疗效和预后更佳。本研究通过对OSA患者的横断面及治疗跟踪，并结合表观遗传学等方法，探讨交感神经系统中介OSA高血压共病的表观遗传学机制，为防治OSA相关的高血压提供新的线索。

阻塞性睡眠呼吸暂停（Obstructive sleep apnea，OSA）及短睡均是高血压患病的独立风险因素，交感神经系统可能是共有的病理生理学机制并受到遗传因素调节。本项目紧密围绕这一关键问题，应用具有国际前沿水平的研究技术，采用多模态的研究策略，从疾病特征、血压调节、血液生化及基因遗传等方面对不同睡眠时间的对照和OSA患者进行独立及比较分析。建立了睡眠时间与OSA防治的综合数据库；阐明了睡眠时间缩短的OSA患者高血压共病与交感神经系统活性的关系及相关基因调控；明确了延长睡眠时间合并持续气道正压通气治疗对睡眠时间缩短的OSA患者治疗的优越性。为深入了解OSA的病理机制及临床评估和寻找有效治疗的生物靶标奠定理论基础及提供指导方向。