5-羟色胺2受体激动剂及拮抗剂对大鼠睡眠呼吸暂停的影响

Effects of 5-HT2 agonist/antagonist on sleep apnea in Sprague-Dawley rats

目的 研究5-羟色胺2（5-HT2）受体激动剂及拮抗剂对SD大鼠睡眠呼吸暂停的影响.方法 将20只成年雄性SD大鼠以随机数字表法分为激动剂组与拮抗剂组,每组10只,均行手术安放脑电及肌电电极,并在第Ⅳ脑室安放微注射套管.术后恢复一周,进行睡眠呼吸监测,连续3 d.第1天不给予任何处理;第2天监测前向第Ⅳ脑室微注射40μl人工脑脊液;第3天监测前向激动剂组大鼠第Ⅳ脑室微注射40μl 5-HT2激动剂（6 mmol/L）,拮抗剂组微注射40μl 5-HT2拮抗剂（2 mmol/L）.结果 以第1天的空白监测和第2天的微注射人工脑脊液后监测作为对照,与前2天相比,激动剂组大鼠总呼吸暂停指数从18.3 次/h和15.2 次/h降至10.8 次/h;非快动眼睡眠期（NREM）和快动眼睡眠期（REM）叹息后呼吸暂停指数（post-sign apnea index,PSAI）均降低,NREM期的自发呼吸暂停指数（spontaneous apnea index,SPAI）也降低（均P〈0.05）;而REM期SPAI的变化无统计学意义（P〉0.05）.总睡眠时间占监测时间的百分比和NREM/REM时间比无明显变化.而拮抗剂组大鼠总AI从19.2次/h和19.0次/h降至13.1 次/h（P〈0.05）;其中NREM期和REM期PSAI均降低（均P〈0.05）,而NREM期和REM期SPAI的变化无统计学意义（均P〉0.05）.睡眠效率和NEMR/REM时间比均无明显变化.结论 5-HT2受体激动剂及拮抗剂均可降低大鼠的睡眠呼吸暂停指数,且对睡眠结构无明显影响.表明 5-HT2受体参与睡眠呼吸调控的复杂性,其具体机制有待进一步研究.

Objective To evaluate the effects of 5-HT2 agonist/antagonist Ketanserin on sleep apnea in Sprague-Dawley（SD）rats. Methods 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,40μl ACSF were microinjected into the Ⅳ ventricle of the rats on the second day. On the third day before monitoring,40μl DOI were microinjected into the Ⅳ ventricle of ten rats and 40μl Ketanserin into another ten ones. Results 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 = 0.005and 0.005, respectively）. PSAI during NREM and REM sleep were significantly decreased （P 〈0.05, respectively）. SPAI during NREM and REM sleep were changed withoutstatistically significant（P 〉0.05, respectively）. It also had no effects on sleep efficiency and the time ratio of NREM sleep and REM sleep. Conclusion 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.