5-羟色胺_(1/2)受体拮抗剂米安色林对大鼠睡眠呼吸暂停的影响

Mianserin-5-hydroxy tryptamine 1/2 receptor antagonist suppresses sleep apnea in rat

目的中枢5-羟色胺(5-HT)及其受体在呼吸调控中发挥着重要作用。呼吸调控不稳定可以导致不规则的呼吸以及呼吸暂停的发生。本研究的目的在于探讨5-HT1/2受体在大鼠睡眠呼吸暂停中的作用。方法成年SD大鼠10只,手术埋置脑电、肌电电极和微注射套管。通过体描箱和多导生理仪,监测大鼠脑电、肌电和呼吸。通过微量泵,向第四脑室匀速泵入5-HT1/2受体的拮抗剂米安色林(mianserin)(100μmol/L)40μl,观察大鼠给药前后呼吸暂停的变化。结果大鼠呈现两种呼吸暂停的类型:自发呼吸暂停(spontaneous apnea)和叹息后呼吸暂停(post-sigh apnea)。中枢微注射5-HT1/2受体拮抗剂米安色林减小了慢速眼球运动睡眠(non-rapid eye movements,NREM)和快速眼球运动睡眠(REM)期的叹息后睡眠呼吸暂停(P<0.05),而对NREM和REM期的自发呼吸暂停无影响(P>0.05),对总睡眠呼吸暂停指数也无显著影响(P>0.05)。在睡眠结构方面,米安色林对睡眠效率及睡眠结构无显著影响(P>0.05)。结论 5-HT和5-HT1/2受体在呼吸调控网络中扮演重要角色,并与大鼠中枢型呼吸暂停的发生密切相关。5-HT1/2受体的不同亚型既有兴奋性受体,又有抑制性受体。米安色林对5-HT1/2受体的双向调节作用可能导致呼吸暂停减轻。

Objective Central 5-hydroxy tryptamine（5-HT） and 5-HT1/2 receptors are involved in respiratory control. The instability of respiratory control may lead to the occurrence of irregular breathings and apneas. The purpose of this study was to investigate the role of 5-HT and 5-HT1/2 receptors in the pathogenesis of central sleep apneas in rats. Methods Ten adult SD rats were recorded for electroencephalogram（EEG）, electromyogram （EMG） and respiration. Microinjection probes were implanted into the fourth ventricle for perfusion of artificial cerebrospinal fluid （ACSF）, and the 5 HT1/2 receptor 1/2 antagonist mianserin （100 μmol/L） （n = 10）. The effects of microinjections of 5 HT1/2 receptor antagonist on sleep apneas of rats were explored. Results SD rats exhibited two kinds of sleep apnea： spontaneous apnea （SP） and post-sigh apnea （PS）. Compared with the ACSF controls, central mieroinjections of 5 HT1/2 receptor antagonist mianserin decreased post-sigh apneas（PS） in NREM and REM sleep（ P 〈 0.05） ,while it had no significant effect on spontaneous apneas（SP） （ P 〉0.05）. It did not change the sleep structure and sleep efficiency of rats as well, compared to ASCF and blank controls. Conclusion 5-HT and 5-HT1/2 receptors played a critical role in the respiratory network and correlated closely with the occurrence of central sleep apneas of rats. Manipulation of 5-HT1/2 receptors could alleviate sleep apneas. An understanding of the molecular mechanisms of sleep apnea syndrome may provide pharmacologic strategies for this prevalent disorder.