Stud for the mechanism of aging and anesthesia-related sleep disorder and its treatment.

研究衰老和麻醉相关睡眠障碍的机制及其治疗。

• 批准号: 21390430
• 负责人: HIROTA Kazuyoshi
• 金额: $ 8.99万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390430/
• 关键词: 睡眠障害; 加齢; ラット; 全身麻酔; 神経生理活性物質; 鎮静; オピオイド

In this study, although age-related sleep disorder was confirmed in rats, we could not recognize a difference with the length of each sleep stage between adult and aged rats. Then, we also studied post-anesthesia sleep disorder and determine the difference of sleep disorder after both type(GABA_A receptor activation[GABA type] or NMDA receptor inhibition[NMDA-type]) of anesthetic agent-induced anesthesia. We found that REM sleep significantly increased a few days after ketamine (NMDA-type) anesthesia while no significant differences in each sleep stage between pre- and post propofol anesthesia were observed. Ketamine-induced post-anesthesia sleep disorder is similar to post-surgical sleep disorder that is considered as a main factor of postoperative respiratory and cardiovascular complications. Thus, ketamine-induced post-anesthesia sleep disorder may be used as a post-surgical sleep disorder model. In addition, this post-anesthesia sleep disorder was almost fully antagonized by icv orexin A or neuropeptide S. If prexin A or neuropeptide S analogues that are un-metabolized in the plasma and penetrated into blood brain barrier after their systemic administration will be developed, we may be able to treat post-surgical sleep disorder.

在这项研究中，虽然年龄相关性睡眠障碍在大鼠中得到证实，但我们无法识别成年大鼠和老年大鼠之间每个睡眠阶段的长度的差异。然后，我们还研究了麻醉后睡眠障碍，并确定了麻醉剂诱导麻醉两种类型(GABAA受体激活[GABA型]或NMDA受体抑制[NMDA型])后睡眠障碍的差异。我们发现，氯胺酮(NMDA型)麻醉后几天，REM睡眠显着增加，而异丙酚麻醉前后各睡眠阶段的变化没有显着差异。氯胺酮引起的麻醉后睡眠障碍类似于手术后睡眠障碍，后者被认为是术后呼吸系统和心血管并发症的主要因素。因此，氯胺酮诱导的麻醉后睡眠障碍可作为手术后睡眠障碍的模型。此外，这种麻醉后睡眠障碍几乎完全被脑室注射增食欲素A或神经肽S所拮抗。如果前体素A或神经肽S类似物在血浆中不代谢，全身给药后穿透血脑屏障，我们可能能够治疗手术后睡眠障碍。

项目成果

Orexin A attenuates sleep-disturbance following ketamine Anesthesia

食欲素 A 可减轻氯胺酮麻醉后的睡眠障碍

• 发表时间: 2009
• 作者: Takeda;Y.;Takada;Y.;Omote;K.;Matsuo;K.;Kushikata T
• 通讯作者: Kushikata T

Nitrous oxide and xenon increase noradrenaline release in the cerebral cortex in vivo and in vitro

一氧化二氮和氙增加体内和体外大脑皮层去甲肾上腺素的释放

• DOI: 10.1016/j.neulet.2009.11.074
• 发表时间: 2010
• 期刊: Neurosci Lett
• 影响因子: 2.5
• 作者: Yoshida H;Kushikata T;Tose R;Kudo M;Kudo T;Hirota K
• 通讯作者: Hirota K

The role of orexin in regulating general anesthesia

食欲素在调节全身麻醉中的作用

• 发表时间: 2010
• 作者: 伊東久勝;池上大悟;山崎光章;成田年;Yoshida H
• 通讯作者: Yoshida H

Orexin decreased ketamine anesthesia-induced sleep disturbance

食欲素减少氯胺酮麻醉引起的睡眠障碍

• 发表时间: 2010
• 作者: Kushikata T;Oishi M;Moriya K;Saito C;Yoshida H;Hirota K
• 通讯作者: Hirota K

Ketamine affects brain orexin A contents in rats

氯胺酮对大鼠脑内食欲素A含量的影响

• 发表时间: 2010
• 作者: Oishi M;Moriya K;Saito C;Kudo M;Kushikata T;Hirota K
• 通讯作者: Hirota K