Department of Pulmonary Medicine, Peking University People's Hospital, Beijing, China.
Sleep Breath. 2012 Mar;16(1):241-5. doi: 10.1007/s11325-011-0489-x. Epub 2011 Feb 12.
Narcolepsy is a debilitating sleep disorder characterized by excessive daytime sleepiness, cataplexy and intrusive REM sleep. Deficits in endogenous orexins are a major pathogenic component of the disease. This disorder is also associated with the gene marker, HLADQB1*0602. An increased prevalence of sleep apnea in narcolepsy suggested interactions among ventilatory chemosensitivity, narcolepsy-cataplexy, and sleep apnea.
Evidence from animal studies using orexin knockout mice and focal microdialysis of an orexin receptor antagonist demostrated that orexins are also contributed to respiratory regulation in a vigilance state-dependent manner, as animals with orexins dysregulation have attenuated hypercapnic ventilatory responses predominately in wakefulness, which is consistent with the notion that the activity of orexinergic neurons is higher during wake than sleep periods. Human model of hypocretin deficiency is patients with narcolepsy-cataplexy. In contrast to findings suggested by animal studies, we found significant decrease in hypoxic responsiveness but not in hypercapnic responsiveness in narcoleptics, and further analysis indicated that decreased ventilatory responses to hypoxia in human narcolepsy-cataplexy is in relation to HLA-DQB1*0602 status, not hypocretin deficiency.
Unlike in mouse, hypocretin-1 is not a major factor contributing to chemoresponsiveness in human. Species differences may exist.
发作性睡病是一种使人虚弱的睡眠障碍，其特征是白天过度嗜睡、猝倒和 REM 睡眠入侵。内源性食欲素的缺乏是该病的一个主要发病因素。这种疾病也与基因标志物 HLADQB1*0602 有关。发作性睡病患者中睡眠呼吸暂停的患病率增加表明通气化学敏感性、发作性睡病猝倒和睡眠呼吸暂停之间存在相互作用。
使用食欲素敲除小鼠的动物研究和食欲素受体拮抗剂的局部微透析的证据表明，食欲素也以警觉状态依赖的方式有助于呼吸调节，因为食欲素失调的动物在清醒时主要减弱了高碳酸血症通气反应，这与食欲素能神经元在觉醒期比睡眠期活动更高的观点一致。人类的食欲素缺乏模型是发作性睡病猝倒患者。与动物研究的发现相反，我们发现发作性睡病猝倒患者的低氧反应性显著降低，但高碳酸血症反应性没有降低，进一步的分析表明，人类发作性睡病猝倒患者的低氧通气反应降低与 HLA-DQB1*0602 状态有关，而与食欲素缺乏无关。
与小鼠不同，食欲素-1不是人类化学反应性的主要因素。可能存在种间差异。
