呼吸兴奋剂多沙普仑促进全麻觉醒的作用和机制研究

General anesthesia has been widely used in clinics, while its mechanism is not fully clear. Delayed emergence from general anesthesia happens from time to time, which increases the occurrence of complications and economic burden of patients. The analeptics currently used in clinic have relatively severe side effects. Recently, studies have shown that orexin can facilitate emergence from general anesthesia. Because of its complex chemical structure and difficulty of synthetic process, a mountain of works needs to be done before its use in clinics. Doxapram has been widely used as a respiratory stimulant on patients. Recently we found in patient that intravenous injection of doxapram would shorten the emergence time from general anesthesia, while its associated mechanism is unclear. Based on our previous discovery that injection of doxapram in patients could increase the plasma level of orexin - A and micro-injection orexin receptor antagonist into animal brain could hinder back the facilitating effect of doxapram on emergence from general anesthesia, we hypothesized that doxapram probably facilitate emergence from general anesthesia by promoting orexin release. This project will use the a series of approaches such as electrophysiology, micro-injection, micro-dialysis and immunohistochemical to further clarity the effect and mechanism of respiratory stimulant doxapram on facilitation of emergence from general anesthesia in animal experiment. The results of the study will lay a theoretic foundation for the new application of doxapram and provide a new thought for developing new medicine.

全身麻醉在临床广泛应用，但其机制尚不完全清楚。麻醉诱导后的苏醒延迟时有发生，增加了并发症，加重了患者的经济负担。目前临床常用促醒剂均有较大副作用。最近有研究发现神经肽orexin有促醒作用，但是其化学分子复杂，合成困难，应用到临床还需要漫长的路要走。多沙普仑作为呼吸兴奋剂早在临床广泛使用。新近我们在临床发现，多沙普仑静脉注射对患者具有显著的促醒作用，但其机制还不清楚。基于我们前期发现多沙普仑注射患者血浆orexin-A水平增加和动物脑内微注射orexin受体拮抗剂可减弱多沙普仑的促醒效应的预实验发现，我们提出多沙普仑可能通过促进orexin释放而发挥促醒效应的假说。本项目将利用神经电生理、微注射、微透析和基因敲除、放射免疫、免疫组化等技术，通过动物实验进一步揭示orexin是否介导了多沙普仑的催醒作用及其机制，研究结果将对老药新用奠定基础，为新药研发提供新思路。

全身麻醉在临床广泛应用，但其机制尚不完全清楚。麻醉诱导后的苏醒延迟时有发生，增 加了并发症，加重了患者的经济负担。目前临床常用促醒剂均有较大副作用。最近有研究发现 神经肽orexin有促醒作用，但是其化学分子复杂，合成困难，应用到临床还需要漫长的路要走 。多沙普仑作为呼吸兴奋剂早在临床广泛使用。我们在临床发现，多沙普仑静脉注射对患 者具有显著的促醒作用。我们前期发现多沙普仑注射患者血浆orexin -A水平增加和动物脑内微注射orexin受体拮抗剂可减弱多沙普仑的促醒效应等实验，我 们验证了多沙普仑可能通过促进orexin释放而发挥促醒效应的假说。本项目利用了行为学、形态学等技术，通过动物实验进一步揭示orexin参与了多沙普仑的催醒作用，研究结果将对老药新用奠定基础，为新药研发提供新 思路。