New aspects of the mechanism of emergence from anesthesia -A research for the antagonistic action of orexin, a cerebral excitatory neurotransmitter, against anesthesia-

麻醉苏醒机制的新面貌 -脑兴奋性神经递质食欲素对麻醉的拮抗作用的研究-

基本信息

批准号：
15390472
负责人：
FUKUDA Satoru
金额：
$ 9.41万
依托单位：
University of Fukui (2004-2005)福井医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Orexin has been reported to have the various actions of increases in feeding, maintenance of wakefulness, pain relief as well as activation of sympathetic nervous system. Among these actions of orexin, the maintenance of wakefulness induced by orexins might contribute to the emergence from anesthesia. In the brain, there are various arousal systems such as noradrenergic, cholinergic, histaminergic, serotonergic and dopaminergic systems. It has been reported that the cholinergic arousal system may contribute to the emergence from isoflurane, sevoflurane, propofol and neuroleptanestesia. Thus, we focused on the role of cholinergic system on the emergence from anesthesia in relation to orexinergic system. From our studies, we got the following results. 1) Intraventricular injection of orexin activated the electroencephalogram (EEG) under deep isoflurane anesthesia in the rat. 2) Microinjection of glutamate into the posterior hypothalamus induced EEG arousal through acting on the orexin ne … More urons. 3) The selective destruction of lateral hypothalamus with orexin-saporin decreased the minimum alveolar concentration of isoflurane. 4) Isoflurane dose-dependently increased the efflux of glutamate in the basal forebrain, not in the posterior hypothalamus and the cortex. Further, under isoflurane anesthesia, microinjection of AMPA, a glutamate receptor agonist, dose-dependently increased the efflux of acetylcholine (Ach) from the cortex, suggesting that the anesthetic level of isoflurane may be balanced between the inhibitory action of isoflurane and the excitatory action of glutamate induced by this agent. 5) Under isoflurane anesthesia, microinjection of orexins into the basal forebrain induced the increases in Ach efflux and activated EEG. In addition, the electrical stimulation of the pedunculopontine tegmentum, the origin of cholinergic ascending pathways, increased the cortical Ach efflux and the EEG arousal under isoflurane anesthesia. These actions were antagonized by SB334867, a selective orexin-1 receptor antagonist. From all the findings, we concluded that orexinergic system may contribute to the emergence from anesthesia through cholinergic arousal system. Less

据报道，Orexin具有增加喂养，保持清醒，缓解疼痛以及激活交感神经系统的各种动作。在奥雷蛋白的这些作用中，奥甲蛋白引起的觉醒的维持可能会导致麻醉的出现。在大脑中，有多种唤醒系统，例如去甲肾上腺素能，胆碱能，组敏能，血清素能和多巴胺能系统。据报道，胆碱能唤醒系统可能会导致异氟烷，七氟醚，提案和Neuroleteptanestesia的出现。因此，我们专注于胆碱能系统在与甲状腺素能系统有关的麻醉中的作用。从我们的研究中，我们得到以下结果。 1）脑室内注射Orexin在大鼠的深度异氟烷麻醉下激活了脑电图（EEG）。 2）将谷氨酸对下丘脑后下丘脑的显微注射通过作用于Orexin ne…更多的ur龙引起的脑电图唤醒。 3）选择性破坏下丘脑横向下丘脑的选择性破坏异氟烷的最小牙槽浓度。 4）异氟烷剂量依赖性地增加了基本前脑中谷氨酸的外排，而不是下丘脑和皮层中的谷氨酸。此外，在异氟烷麻醉下，AMPA的显微注射（一种谷氨酸受体激动剂）剂量依赖性地增加了皮质中乙酰胆碱（ACH）的外排，这表明同甲基硫酸的麻醉水平可能是在异氟烷抑制作用和促成剂量的抑制作用之间平衡的。 5）在异氟烷麻醉下，对基本前脑的微注射诱导ACH外排和活化的脑电图的增加。另外，髓样升天途径的原始刺激的电刺激增加了皮质ACH外排和在异氟烷麻醉下的脑电图唤醒。这些作用被选择性Orexin-1受体拮抗剂SB334867拮抗。从所有发现中，我们得出的结论是，甲素能系统可能导致通过胆碱能唤醒系统的麻醉出现。较少的

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

オレキシン

食欲素

DOI：
发表时间：
2004
期刊：
臨床麻酔 28・8
影响因子：
0
作者：
鈴木久人;安田善一;江口広毅他12名
通讯作者：
江口広毅他12名

Orexin A elicits arousal electroencephalogram without sympathetic cardiovascular activation in isoflurane-anesthetized rats.

Orexin A 在异氟烷麻醉的大鼠中引发唤醒脑电图，但没有交感心血管激活。

DOI：
发表时间：
2003
期刊：
Anesth Analg 97
影响因子：
0
作者：
Yasuda Y;Takeda A;Fukuda S;Suzuki H;Ishimoto M;Mori Y;Eguchi H;Saitoh R;Fujihara H;Honda K;Higuchi T
通讯作者：
Higuchi T

Yasuda Y, Takeda A, Fukuda S, et al.: "Orexin-A elicits arousal electroencephalography without sympathetic cardiovascular activation in isoflurane-anesthetized rats"Anesthesia & Analgesia. 97・6. 1663-1666 (2003)

Yasuda Y、Takeda A、Fukuda S 等人：“Orexin-A 在异氟烷麻醉的大鼠中引发唤醒脑电图，而不激活交感神经心血管”麻醉与镇痛 97・6（2003）。