Zhong Yi-jue, Zhang Cheng, Wang Guang-fa
Department of Pulmonary Medicine, First Hospital, Peking University, Beijing 100034, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2010 May;33(5):350-3.
To evaluate the effects of 5-HT2 agonist/antagonist Ketanserin on sleep apnea in Sprague-Dawley (SD) rats.
Twenty adult male SD rats were operated for implantation of EEG and EMG electrodes and a microinjection probe was placed within the fourth ventricle. After recovery for a week, rats were monitored for sleep and respiration in three continuous days. There is no intervention on the first day. Before monitoring, 40 microl ACSF were microinjected into the IV ventricle of the rats on the second day. On the third day before monitoring, 40 microl DOI were microinjected into the IV ventricle of ten rats and 40 microl Ketanserin into another ten ones.
Compared with blank control and microinjection of ACSF, DOI significantly reduced the total apnea index (AI) from 18.3 (11.1, 20.3) times/h and 15.2 (11.4, 18.0) times/h to 10.8 (3.1, 14.1) times/h (P=0.005 and 0.005, respectively). Post sign apnea index (PSAI) during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep as well as spontaneous apnea index (SPAI) during NREM sleep were all significantly decreased; (P<0.05, respectively); while it had no effect on SPAI during REM sleep (P>0.05). Neither sleep efficiency (the percent of total sleep time in total monitoring time) nor the time ratio of NREM sleep and REM sleep was significantly changed. In contrast to blank control and microinjection of ACSF, Ketanserin significantly reduced the total apnea index (AI) from 19.2 (13.7, 20.9) times/h and 19.0 (12.9, 21.6) times/h to 13.1 (9.5, 14.9) times/h (P=0.005 and 0.005, respectively). PSAI during NREM and REM sleep were significantly decreased (P<0.05, respectively). SPAI during NREM and REM sleep were changed without statistically significant (P>0.05, respectively). It also had no effects on sleep efficiency and the time ratio of NREM sleep and REM sleep.
Both 5-HT2 agonist and antagonist decreased the sleep apnea index and had no effects on sleep structure. It shows that the role of 5-HT2 receptor in the respiratory regulation during sleep is complex. The mechanisms involved remain to be studied in future.
评估5-羟色胺2(5-HT2)激动剂/拮抗剂酮色林对斯普拉格-道利(SD)大鼠睡眠呼吸暂停的影响。
20只成年雄性SD大鼠接受手术,植入脑电图(EEG)和肌电图(EMG)电极,并在第四脑室内放置微量注射探头。恢复一周后,连续三天监测大鼠的睡眠和呼吸情况。第一天不进行干预。在第二天监测前,向大鼠第四脑室内微量注射40微升人工脑脊液(ACSF)。在第三天监测前,向10只大鼠的第四脑室内微量注射40微升DOI,向另外10只大鼠的第四脑室内微量注射40微升酮色林。
与空白对照组和微量注射ACSF相比,DOI使总呼吸暂停指数(AI)显著降低,从18.3(11.1,20.3)次/小时和15.2(11.4,18.0)次/小时降至10.8(3.1,14.1)次/小时(分别为P = 0.005和0.005)。非快速眼动(NREM)睡眠和快速眼动(REM)睡眠期间的后信号呼吸暂停指数(PSAI)以及NREM睡眠期间的自发呼吸暂停指数(SPAI)均显著降低(分别为P < 0.05);而对REM睡眠期间的SPAI无影响(P > 0.05)。睡眠效率(总睡眠时间占总监测时间的百分比)以及NREM睡眠与REM睡眠的时间比均无显著变化。与空白对照组和微量注射ACSF相比,酮色林使总呼吸暂停指数(AI)显著降低,从19.2(13.7,20.9)次/小时和19.0(12.9,21.6)次/小时降至13.1(9.5,14.9)次/小时(分别为P = 0.005和0.005)。NREM和REM睡眠期间的PSAI均显著降低(分别为P < 0.05)。NREM和REM睡眠期间的SPAI变化无统计学意义(分别为P > 0.05)。对睡眠效率以及NREM睡眠与REM睡眠的时间比也无影响。
5-HT2激动剂和拮抗剂均降低了睡眠呼吸暂停指数,且对睡眠结构无影响。这表明5-HT2受体在睡眠期间呼吸调节中的作用较为复杂。其涉及的机制有待未来进一步研究。