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外周化学感受器在睡眠呼吸障碍时对间歇性低氧适应不良反应的机制

冯文龙, 郑颜儿, 梁宝成

香港大学李嘉诚医学院生理学系；解剖学系；心、脑、内分泌及抗衰老研究中心，香港

摘要

颈动脉体外周化学感受器在化学刺激从动脉血到中枢的传导及相应的化学反射的诱发过程中起到重要作用，在此过程中介导了低氧条件下的通气及循环反应。颈动脉化学感受器活性的调节对于高海拔地区通气适应性起着显著作用。此外，颈动脉化学感受器的活性在患有睡眠呼吸障碍疾病的患者中显著增强，尤其在患有中枢神经性呼吸暂停综合征或阻塞性睡眠呼吸暂停综合征的患者中以及相关的实验动物身上尤为突出。因此，颈动脉体发挥功能以保持氧动态平衡，而异常的颈动脉化学感受器活性可在睡眠呼吸暂停时表现出适应性或者致病性的特性。本文旨在总结间歇性低氧引起化学感受器活性增强过程中的细胞机制和分子机制。我们最近的研究显示颈动脉体中的肾素-血管紧张素系统在过度的化学反射活性时被上调，其所介导的炎症亦具有致病效用。这些调节机制在低氧诱发的颈动脉体功能适应不良变化中发挥重要功能，这会在睡眠呼吸暂停综合征的病理生理机制中发挥显著作用。

关键词： 血管紧张素; 颈动脉体; 炎症; 阻塞性睡眠呼吸暂停综合征

分类号：R339.17+2

Mechanisms of maladaptive responses of peripheral chemoreceptors to intermittent hypoxia in sleep-disordered breathing

Man Lung Fung, George Lim Tipoe, Po Sing Leung

Department of Physiology； Department of Anatomy； Research Centre of Heart, Brain, Hormone &

Abstract

Peripheral chemoreceptors in the carotid body play important roles in the transduction of chemical stimuli in the arterial blood to the central for eliciting the chemoreflex, which mediates the ventilatory and circulatory responses to hypoxia. The activity of carotid chemoreceptor is modulated and significantly contributes to the ventilatory acclimatization at high altitude. In addition, the carotid chemoreceptor activity is augmented in patients with sleep-disordered breathing, notably in central or obstructive sleep apnea, and also in experimental animals. Thus, the carotid body functions to maintain the oxygen homeostasis, whereas anomalous carotid chemoreceptor activities could be both adaptive and pathogenic in sleep apnea. This review aims to summarize the cellular and molecular mechanisms that could mediate the augmented chemoreceptor activity induced by intermittent hypoxia. Our recent findings suggest a pathogenic role of inflammation mediated by an upregulation of renin-angiotensin system in the carotid body in the over-activity of the chemoreflex. These locally regulated mechanisms are proposed to be a significant part of the hypoxia-mediated maladaptive changes of the carotid body function, which could play a role in the pathophysiology of sleep apnea.

Key words: angiotensin; carotid body; inflammation; obstructive sleep apnea

收稿日期：　　录用日期：

通讯作者：冯文龙　　E-mail: fungml@hku.hk

引用本文：

冯文龙, 郑颜儿, 梁宝成. 外周化学感受器在睡眠呼吸障碍时对间歇性低氧适应不良反应的机制[J]. 生理学报 2014; 66 (1): 23-29.

Man Lung Fung, George Lim Tipoe, Po Sing Leung. Mechanisms of maladaptive responses of peripheral chemoreceptors to intermittent hypoxia in sleep-disordered breathing. Acta Physiol Sin 2014; 66 (1): 23-29 (in Chinese with English abstract).