Role of orexin in sleep disorder after isoflurane anesthesia in rats

Objective To evaluate the role of orexin in the sleep disorder after isoflurane anesthesia in rats.Methods Sixty-four male Sprague-Dawley rats,aged 10-12 weeks,weighing 280-320 g,were randomly divided into 2 groups (n =32 each) using a random number table:control group (C) and isoflurane group (Ⅰ).Group Ⅰ inhaled 1.2％ isoflurane from 8:00 to 13:30 to induce anesthesia,followed by 0.5 h of recovery.Group C received no anesthesia and the other procedures were similar to those previously described in group Ⅰ.The induction time and awakening time were recorded.Eight rats were randomly chosen to record the movement condition (locomotor time and activity) from 14:00 to 8:00 the next morning.Before beginning of anesthesia,at 4 h after beginning of anesthesia,and at 4 and 10 h after the end of anesthesia,6 rats were randomly chosen in each group to count the orexin/c-fos double-labeled neurons in hypothalamus.The ratio of activated orexin neurons (orexin/c-fos double-labeled neurons to orexin positive neurons) was calculated and plasma orexin-A concentration was detected.Results The induction time was (2.14 ± 0.17) min,awakening time was (8.7 ± 0.5) min,and EEG showed that there was no typical burst and suppression patterns in group Ⅰ.There was no significant difference in the number of orexin positive neurons between the two groups (P ＞ 0.05).Compared with group C,the time for locomotor activity was significantly prolonged,and the activity was increased during the night (P ＜ 0.01),the number of activated neurons,ratio of activated orexin neurons and plasma orexin-A concentration were decreased at 4 h after beginning of anesthesia in group Ⅰ (P ＜ 0.01).The plasma orexin-A concentration was lower at 4 h after beginning of anesthesia,while higher at 10 h after the end of anesthesia than before beginning of anesthesia in group Ⅰ (P ＜ 0.05).The number of activated neurons was significantly larger and ratio of activated orexin neurons was higher before beginning of anesthesia and at 10 h after the end of anesthesia and the plasma orexin-A concentration was higher at 4 and 10 h after the end of anesthesia than at 4 h after beginning of anesthesia in group Ⅰ (P ＜ 0.05 or 0.01).Conclusion The development of sleep disorder after isoflurane anesthesia during the day time in rats is related to the regulatory role of orexin in it. Key words: Sleep initiation and maintenance disorders;  Isoflurane;  Orexin