The role of 5-HT and 5-HT2A receptors in the occurrence of central sleep apnea in rats
首发时间:2014-12-12
Abstract:Central serotonin (5-HT) and 5-HT2A 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-HT2A receptors in the pathogenesis of central sleep apneas in rats. The rats were recorded for electroencephalogram(EEG), electromyogram (EMG) and respiration. 5-HT2A protein content of 27 rats' brainstems were detected by western blot and their relationship with sleep apneas were analyzed. Microdialysis probes were implanted into the fourth ventricle for perfusion of artificial cerebrospinal fluid, serotonin (10mM) (n=8) and the serotonin receptor 2A antagonist mianserin (100μM) (n=10). The effects of microinjections of 5-HT and 5-HT2A receptor antagonists on sleep apneas of rats were explored. 5-HT2A protein content correlated negatively with post-sigh apneas in NREM and REM sleep (r= -0.663, -0.452, respectively, P<0.05). Compared with the ACSF controls, 5-HT microinjections in the fourth ventricle decreased post-sigh and spontaneous sleep apneas only in NREM sleep (P<0.05), while central microinjections of 5-HT2A receptor antagonist mianserin decreased post-sigh apneas in NREM and REM sleep (P<0.05). 5-HT and 5-HT2A receptors played a critical role in the respiratory network and correlated closely with the occurrence of central sleep apneas of rats. Increasing central 5-HT concentration could reduce sleep apneas, while manipulation of 5-HT2A receptors could also alleviate sleep apneas. An understanding of the molecular mechanisms of sleep apnea syndrome may provide pharmacologic strategies for this prevalent disorder.
keywords: sleep apnea respiratory control serotonin 5-HT2A receptor
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5-HT以及5-HT2A受体在大鼠中枢型睡眠呼吸暂停中的作用
摘要:5-HT以及5-HT2A受体参与了中枢的呼吸调控。呼吸调控的不稳定将导致不规则的呼吸和呼吸暂停。本研究的目的是探讨5-HT和5-HT2A受体在大鼠中枢型睡眠呼吸暂停发生中的病理生理机制。通过多导生理仪记录大鼠的脑电、肌电和呼吸。通过western blot 的方法检测大鼠脑干5-HT2A 受体蛋白的表达(n=27)。通过第四脑室微注射的方法给予5-HT(10mM) (n=8)以及5-HT2A受体拮抗剂米胺色林(100μM) (n=10),观察其对大鼠睡眠呼吸暂停的影响。结果显示:大鼠脑干呼吸中枢的5-HT2A 受体的表达量与大鼠非快动眼睡眠(NREM)期和快动眼睡眠(REM)期的叹息后呼吸暂停(post-sigh apnea)成反比(r= -0.663, -0.452, respectively, P<0.05)。与对照组(注射人工脑脊液)相比,第四脑室注射5-HT减少了大鼠非快动眼睡眠(NREM)期的呼吸暂停,包括叹息后呼吸暂停(post-sigh apnea)和自发呼吸暂停(spontaneous apnea)(P<0.05); 而第四脑室注射5-HT2A受体拮抗剂米胺色林则减少了非快动眼睡眠(NREM)及快动眼睡眠(REM)期的叹息后呼吸暂停(post-sigh apnea)(P<0.05)。故提高中枢5-HT的浓度可以减轻NREM期的呼吸暂停;而拮抗5-HT2A受体则减少了呼吸暂停的一种-叹息后呼吸暂停。因此,5-HT以及5-HT2A受体在整个呼吸网络中发挥着重要作用并与大鼠中枢型呼吸暂停的发生密切相关。但其具体的调控通路仍有待明确。对睡眠呼吸紊乱发病分子机制的探讨将为药物研发提供依据。
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No.4622152102072114****
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