权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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，食欲素具有增加摄食、维持清醒、缓解疼痛以及激活交感神经系统的各种作用。在食欲素的这些作用中，食欲素诱导的清醒状态的维持可能有助于麻醉的苏醒。在大脑中，有多种唤醒系统，如去甲肾上腺素、胆碱、组胺、5-羟色胺和多巴胺能系统。据报道，胆碱能觉醒系统可能与异氟醚、七氟醚、异丙酚和神经衰弱的出现有关。因此，我们将重点放在与食欲素能系统有关的麻醉苏醒过程中胆碱能系统的作用。从我们的研究中，我们得到了以下结果。1)脑室注射增食欲素可激活异氟醚麻醉大鼠的脑电活动。2)下丘脑后部微量注射谷氨酸通过作用于增食欲素…而引起脑电觉醒。更多的玉米粉。3)选择性损毁下丘脑外侧核可降低异氟醚的最低肺泡浓度。4)异氟醚可剂量依赖性地增加谷氨酸在基底前脑的外流，但不能增加下丘脑后部和皮质的谷氨酸外流。此外，在异氟醚麻醉下，微量注射谷氨酸受体激动剂AMPA可剂量依赖性地增加大脑皮层乙酰胆碱(Ach)的外流，提示异氟醚的麻醉水平可能在异氟醚的抑制作用和谷氨酸的兴奋作用之间达到平衡。5)异氟醚麻醉下，基底前脑内微量注射食欲素可引起Ach流出量增加，激活脑电。此外，在异氟醚麻醉下，电刺激胆碱能上行通路的起点--桥脑被盖，可增加皮层Ach流出和脑电觉醒。这些作用可被选择性食欲素-1受体拮抗剂SB334867所拮抗。以上结果提示，食欲素能系统可能通过胆碱能觉醒系统参与麻醉苏醒。较少

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）。