乙酰唑胺对高原常住居民睡眠呼吸障碍的治疗与作用机制

同低海拔人群比较，高原常住居民中阻塞性睡眠呼吸暂停（OSA）的患病率和严重程度显著增高，同时存在的持续性和间歇性低氧会进一步增加心血管疾病的风险。因此，探索较传统方式更具针对性和方便的药物治疗尤为必要。高质量随机对照研究表明，乙酰唑胺能有效降低急性海拔升高所致的OSA严重程度增加和血压升高，但缺乏针对高原常住居民治疗作用的探索；其作用机制可能与改善OSA患者在低压低氧环境下的通气控制不稳定性和体液转移量有关，但尚未对该假说进行系统研究。项目申请人前期重要工作发现，夜间氧疗可有效治疗高原OSA和降低血压，通气控制不稳定性的改善可能是其重要机制。本项目将在探索高原常住居民OSA及血压特征的基础上，明确乙酰唑胺对其治疗作用；同时，采用重复呼吸与生物电阻抗技术，测量通气控制不稳定性和体液转移量，进行相应的机制研究。研究将增加对高原OSA病理生理学发生机制的了解，为干预策略提供新的直接证据。

The prevalence and severity of obstructive sleep apnea (OSA) in highland permanent residents was significantly higher compared to lowland residents. The presence of both sustained and intermittent hypoxia would further increase the risk of cardiovascular disease. Therefore, it is particularly necessary to explore more targeted and convenient drug treatment than traditional ones. High quality randomized controlled trial found that acetazolamide could effectively dampen the increase of OSA severity and blood pressure induced by altitude ascent, however, there is no study to explore the effect of acetazolamide on highland permanent residents. The possible mechanism may be related to the improvement of ventilation control instability and fluid shift in OSA patients under hypobaric hypoxia, but the hypothesis has not been systematically studied. The applicant previous important studies found that nocturnal oxygen supplementation could effectively treat highland OSA and reduce blood pressure, the improvement of ventilation control instability may be the possible mechanism. The study will base on the exploration of OSA and blood pressure characteristics in highland permanent residents to clarify the treatment effect of acetazolamide; and to further explore the related mechanisms through the ventilation control stability and fluid shift measured by rebreathing method and bioelectrical impedance technology. This study will increase the understanding of the OSA pathophysiology at high altitude and provide new direct evidence for intervention strategies.