Zhang Li-Na, Yang Cen, Ouyang Peng-Rong, Zhang Zhi-Chao, Ran Ming-Zi, Tong Li, Dong Hai-Long, Liu Yong
Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases, Education Ministry, Xian Jiaotong University School of Medicine, China.
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, China.
Neuropeptides. 2016 Aug;58:7-14. doi: 10.1016/j.npep.2016.02.003. Epub 2016 Feb 16.
Previous studies have demonstrated that orexinergic neurons involve in promoting emergence from anesthesia of propofol, an intravenous anesthetics, while whether both of orexin-A and orexin-B have promotive action on emergence via mediation of basal forebrain (BF) in isoflurane anesthesia has not been elucidated. In this study, we observed c-Fos expressions in orexinergic neurons following isoflurane inhalation (for 0, 30, 60, and 120min) and at the time when the righting reflex returned after the cessation of anesthesia. The plasma concentrations of orexin-A and -B in anesthesia-arousal process were measured by radioimmunoassay. Orexin-A and -B (30 or 100pmol) or the orexin receptor-1 and -2 antagonist SB-334867A and TCS-OX2-29 (5 or 20μg) were microinjected into the basal forebrain respectively. The effects of them on the induction (loss of the righting reflex) and the emergence time (return of the righting reflex) under isoflurane anesthesia were observed. The results showed that the numbers of c-Fos-immunoreactive orexinergic neurons in the hypothalamus decreased over time with continued isoflurane inhalation, but restored at emergence. Similar alterations were observed in changes of plasma orexin-A concentrations but not in orexin-B during emergence. Administration of orexins had no effect on the induction time, but orexin-A facilitated the emergence of rats from isoflurane anesthesia while orexin-B didn't. Conversely, microinjection of the orexin receptor-1 antagonist SB-334867A delayed emergence from isoflurane anesthesia. The results indicate that orexin-A plays a promotive role in the emergence of isoflurane anesthesia and this effect is mediated by the basal forebrain.
以往研究表明，食欲素能神经元参与促进静脉麻醉药丙泊酚麻醉苏醒，而异氟烷麻醉时，食欲素A和食欲素B是否均通过基底前脑介导对苏醒有促进作用尚未阐明。本研究观察了异氟烷吸入（0、30、60和120分钟）及麻醉停止后翻正反射恢复时食欲素能神经元中c-Fos的表达。采用放射免疫分析法测定麻醉-苏醒过程中血浆食欲素A和B的浓度。分别将食欲素A和B（30或100 pmol）或食欲素受体1和2拮抗剂SB-334867A和TCS-OX2-29（5或20 μg）微量注射到基底前脑。观察它们对异氟烷麻醉下诱导期（翻正反射消失）和苏醒时间（翻正反射恢复）的影响。结果显示，随着异氟烷持续吸入，下丘脑c-Fos免疫反应性食欲素能神经元数量随时间减少，但在苏醒时恢复。苏醒过程中血浆食欲素A浓度变化呈现类似改变，而食欲素B未出现此变化。给予食欲素对诱导时间无影响，但食欲素A促进大鼠从异氟烷麻醉中苏醒，而食欲素B则无此作用。相反，微量注射食欲素受体1拮抗剂SB-334867A延迟了大鼠从异氟烷麻醉中的苏醒。结果表明，食欲素A在异氟烷麻醉苏醒中起促进作用，且该作用由基底前脑介导。
