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反复吸入七氟醚通过 GABAA 受体 ε 亚基抑制新生小鼠浦肯野细胞的信息传递并延迟运动发育。

Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice.

机构信息

Department of Anesthesiology, The Affiliated Heji Hospital of Changzhi Medical College, Changzhi, Shanxi 046011, P.R. China.

Department of Anesthesiology, The Suburban People's Hospital, Changzhi, Shanxi 046011, P.R. China.

出版信息

Mol Med Rep. 2018 Jan;17(1):1083-1092. doi: 10.3892/mmr.2017.7941. Epub 2017 Nov 3.

Abstract

General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear. In the present study, neonatal mice received repeated inhalation of sevoflurane, and electrophysiological alterations in Purkinje cells (PCs) and the development of motor functions were detected. In addition, γ‑aminobutyric acidA receptor ε (GABAA‑R ε) subunit knockout mice were used to investigate the mechanism of action of sevoflurane on cerebellar function. In the neonatal mice, the field potential response of PCs induced by sensory stimulation and the motor function indices were markedly inhibited by sevoflurane, and the inhibitory effect was positively associated with the number of repetitions of anesthesia. In additional the GABAA‑R ε subunit level of PCs was promoted by sevoflurane in a dose‑dependent manner, and the inhibitory effects of sevoflurane on PC field potential response and motor function were alleviated in GABAA‑R ε subunit knockout mice. The GABAA‑R ε subunit was activated by sevoflurane, leading to inhibition of sensory information transmission in the cerebellar cortex, field potential responses of PCs and the development of cerebellar motor function. The present study provided experimental evidence for the safe usage of sevoflurane in clinical anesthesia, and suggested that GABAA‑R ε subunit antagonists may be considered for combined application with general anesthesia with repeated inhalation of sevoflurane, for adverse effect prevention in the clinic.

摘要

全身麻醉广泛应用于小儿外科手术中,但其对小脑信息传递和运动功能的影响尚不清楚。在本研究中,新生小鼠反复吸入七氟醚,检测浦肯野细胞(PCs)的电生理改变和运动功能的发育情况。此外,还使用γ-氨基丁酸 A 受体 ε(GABAA-R ε)亚基敲除小鼠来研究七氟醚对小脑功能的作用机制。在新生小鼠中,感觉刺激诱导的 PCs 场电位反应和运动功能指标明显被七氟醚抑制,且抑制作用与麻醉重复次数呈正相关。此外,七氟醚呈剂量依赖性地促进 PCs 中 GABAA-R ε亚基的水平,GABAA-R ε 亚基敲除小鼠中七氟醚对 PCs 场电位反应和运动功能的抑制作用减轻。七氟醚激活 GABAA-R ε 亚基,导致小脑皮质感觉信息传递、PCs 场电位反应和小脑运动功能的发育受到抑制。本研究为临床麻醉中使用七氟醚的安全性提供了实验依据,并提示 GABAA-R ε 亚基拮抗剂可能考虑与重复吸入七氟醚的全身麻醉联合应用,以预防临床不良反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9da6/5780070/993f49e67621/MMR-17-01-1083-g00.jpg

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