Circadian gene expression is suppressed during sevoflurane anesthesia and the suppression persists after awakening
Circadian gene expression is suppressed during sevoflurane anesthesia and the suppression persists after awakening
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DOI：
10.1016/j.brainres.2007.09.011
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发表时间：
2007-12-14
期刊：
影响因子：
2.9
通讯作者：
Sakamoto, Atsuhiro
中科院分区：
文献类型：
--
作者：
Kobayashi, Katsuya;Takemori, Ken;Sakamoto, Atsuhiro
全身麻醉是一种常规的外科手术，其安全性已得到临床结果的认可；然而，其在分子水平上的作用尚未阐明。我们之前的研究表明，吸入麻醉会影响10000个基因中1.5%的表达，其中包括所谓的昼夜节律基因。在目前的研究中，我们证实吸入七氟醚改变了昼夜节律基因的表达，并调查了这种改变在从麻醉中苏醒后是否持续。用4.0%七氟醚麻醉大鼠0、2、6h，每组9只，然后处死。大鼠同样麻醉6h，麻醉后恢复，清醒后2，6，24 h处死(每组9只)。各组均开始麻醉，于13：00处死所有大鼠，用实时荧光定量RT-PCR方法检测全脑基因表达。吸入七氟醚2 h和6 h后，PER2、DBP、Arc、Egr1、Krox20和NGFI-B基因的表达均受到抑制，苏醒后PER2、DBP、Arc、Egr1、Krox20和NGFI-B基因的表达均受到抑制，但恢复24 h后，除Krox20基因外，其余基因的表达水平均显著低于对照组。我们证明在七氟醚麻醉期间，昼夜节律基因的表达在整个大脑中受到抑制，并且这种抑制在七氟醚治疗结束后至少持续24小时。这表明七氟醚麻醉可能会在分子水平上产生影响，而且这些影响是长期的。(C)2007 Elsevier B.V.保留所有权利。
General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. We previously showed that inhalation anesthesia affects the expression of 1.5% of 10,000 genes, which included so-called circadian genes. In the current study, we confirmed that inhalation of sevoflurane alters circadian gene expression, and investigated whether this alteration persists after awakening from anesthesia. Rats were anesthetized with 4.0% sevoflurane for 0 h, 2 h and 6 h (n = 9 each group), before being sacrificed. Rats were also anesthetized for 6 h and allowed to recover after anesthesia, then sacrificed 2 h, 6 h and 24 h after awakening (n = 9 each group). Anesthesia was started for each group so that all rats would be sacrificed at 13:00, and gene expression in the whole brain was examined using real-time RT-PCR. Expression of the genes encoding Per2, Dbp, Arc, Egr1, Krox20 and NGFI-B was suppressed during inhalation of sevoflurane for 2 h and 6 h. Although the suppression tended to be alleviated after awakening from anesthesia, the expression levels after a recovery period of 24 h remained significantly lower than the control levels of these genes, except for Krox20. We demonstrated that circadian gene expression is suppressed in whole brain during sevoflurane anesthesia, and the suppression continues for at least 24 h after termination of sevoflurane treatment. This suggests that sevoflurane anesthesia may have effects at the molecular level and that these effects are long lasting. (C) 2007 Elsevier B.V. All rights reserved.