中枢组胺能神经系统调节睡眠-觉醒机制研究进展  

Advances in the study of histaminergic systems and sleep-wake regulation

作　　者：刘天雅[1] 洪宗元[1] 曲卫敏[2] 黄志力[2] 

机构地区：[1]皖南医学院定量药理研究所,药理学教研室,安徽芜湖241002 [2]复旦大学上海医学院药理学系,上海200032

出　　处：《药学学报》2011年第3期247-252,共6页Acta Pharmaceutica Sinica

基　　金：教育部科学技术研究重点项目(208058);安徽省自然科学基金资助项目(070413139);国家自然科学基金资助项目(30625021,30821002,30970955,31070957);国家“重大新药创制”科技重大专项(2009ZX09303-006);上海市科委基金(09PJ1401800,09JC1402500,10XD1400400,10441901600);上海市重点学科建设项目(B119)基金

摘　　要：哺乳动物组胺能神经元集中分布于下丘脑后部的结节乳头核(tuberomammillary nucleus,TMN),其神经纤维投射至全脑。研究发现,中枢组胺的释放与觉醒时相呈正相关,觉醒期的释放量是睡眠期的4倍;内源性物质前列腺素E2和神经肽阿立新(orexin)激活TMN组胺能神经元,增加组胺释放,促进觉醒;前列腺素D2和腺苷抑制组胺能神经元活性,诱导睡眠。本文综述组胺能神经系统调节睡眠-觉醒研究进展,讨论拟(抗)组胺类药物用于促觉醒或(和)镇静催眠的可能性。Histaminergic neurons solely originate from the tuberomammillary nucleus（TMN） in the posterior hypothalamus and send widespread projections to the whole brain.Experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes.Endogeneous prostaglandin E2 and orexin activate histaminergic neurons in the TMN to release histamine and promote wakefulness.Conversely,prostaglandin D2 and adenosine inhibit histamine release by increasing GABA release in the TMN to induce sleep.This paper reviews the effects and mechanisms of action of the histaminergic system on sleep-wake regulation,and briefly discusses the possibility of developing novel sedative-hypnotics and wakefulness-promoting drugs related to the histaminergic system.

关 键 词：组胺能神经系统 前列腺素E2 OREXIN 前列腺素D2 腺苷 睡眠-觉醒调节 

分 类 号：R963[医药卫生—微生物与生化药学]