机体和细胞对间歇性低氧的反应与呼吸暂停综合征的关系

摘要

睡眠障碍伴反复性呼吸暂停的患者表现为交感神经活动(sympathetic nerve activity,SNA)增强的自主神经系统功能失调和高血压.动物实验表明反复呼吸暂停引起的慢性间歇性低氧(chronic intermittent hypoxia,CIH)是激发自主神经系统功能失调的主要因素.在啮齿类动物模型中,CIH使动脉化学感受性反射功能增强的部分原因在于增加了颈动脉体对低氧的敏感性,因而导致SNA增强.最近研究表明,缺氧诱导因子1和2( hyproxia-inducible factor,HIF)转录的变化及随之而来的活性氧类介导的信号,是CIH时化学感受性反射引起的交感神经系统兴奋的重要细胞机制.%Patients with sleep-disordered breathing with recurrent apneas exhibit autonomic dysfunction including elevated sympathetic nerve activity (SNA) and hypertension.Studies on experimental animals show that chronic intermittent hypoxia (CIH) resulting from recurrent apneas is a major stimulus for evoking autonomic dysfunction.In rodent models,CIH enhances arterial chemoreflex function in part due to enhanced carotid body sensitivity to hypoxia.The enhanced chemo-reflex leads to elevated sympathetic nerve activity.Recent studies suggest that transcriptional changes involving hypoxiainducible factor-1 and 2 (HIF-1,HIF-2) and the resulting reactive oxygen species-mediated signaling are critical cellular mechanisms underlying the chemoreflex-mediated excitation of sympathetic nervous system by CIH.