Moore Michael W, Akladious Afaf, Hu Yufen, Azzam Sausan, Feng Pingfu, Strohl Kingman P
Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
Louis Stokes Cleveland DVA Medical Center, Cleveland, OH, United States; Neogene Biosciences LLC, Cleveland, OH, United States; Division of Pulmonary, Critical Care, and Sleep Medicine, UH Case Medical Center, Cleveland, OH 44016, United States.
Respir Physiol Neurobiol. 2014 Aug 15;200:118-25. doi: 10.1016/j.resp.2014.03.014. Epub 2014 Jun 11.
The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing.
In C57BL/6J (B6) mice, body plethysmography was performed with and without EEG monitoring of state (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake states at baseline and with an intracerebroventricular administration of vehicle, 4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCS OX2 29.
A significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with the agonist. Expressed as a function of the change from baseline, there was a significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003, f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas during sleep from 29.7±4.7 (M±SEM) to 7.3±2.4 during sleep (p=0.001). There was also a reduction in apneas during wakefulness. Administration of the antagonist did not increase event rate over baseline levels.
The B6 mouse is a preclinical model of wake-and sleep-disordered breathing, and the orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will reduce events in sleep and also wakefulness.
研究假设是食欲素2受体（OX2R）激动剂可预防与睡眠相关的呼吸紊乱。
在C57BL/6J（B6）小鼠中，在有和没有脑电图监测状态（清醒、非快速眼动睡眠和快速眼动睡眠）的情况下进行体容积描记法。观察指标为基线时以及脑室内注射溶媒、4纳摩尔激动剂OB(DL)和4纳摩尔拮抗剂TCS OX2 29后睡眠-清醒状态下每小时的呼吸暂停率。
每小时呼吸暂停次数显著减少（p = 0.035，f = 2.99），尤其是使用激动剂时。以相对于基线变化的函数表示，在清醒（p = 0.03，f = 3.8）、非快速眼动睡眠（p = 0.003，f = 6.98）和快速眼动睡眠（p = 0.03，f = 3.图2）状态下，各实验组之间存在显著差异，激动剂使睡眠期间的呼吸暂停率从29.7±4.7（平均值±标准误）降至睡眠期间的7.3±2.4（p = 0.001）。清醒时的呼吸暂停次数也有所减少。拮抗剂的给药并未使事件发生率高于基线水平。
B6小鼠是清醒和睡眠呼吸紊乱的临床前模型，脑室内给予4纳摩尔剂量的食欲素受体激动剂可减少睡眠和清醒时的事件发生。
