新生小鼠反复吸入七氟醚抑制浦肯野细胞的信息传递并且通过GABAA受体的ε（艾普西龙）亚基减缓运动神经发育
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Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice
背景与目的:尽管全身麻醉对小脑信息传递和运动功能的影响尚不清楚，但是全身麻醉还是广泛应用于小儿外科手术。
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方法：在最新的实验中，新生小鼠反复吸入七氟烷，检测七氟醚对浦肯野细胞（PCs）的电生理改变和运动功能的发育的影响，还做了七氟烷影响敲除了γ-氨基丁酸A受体ε（GABA A-Rε）亚基的小鼠小脑功能机制的研究。
结果：在新生小鼠中，感觉刺激诱发的PCs场电位反应和运动功能指标均明显受到七氟烷的抑制，抑制程度与麻醉重复次数呈正相关。另外，七氟烷以剂量依赖方式增加PCs的GABAA-R ε亚基，在GABAA-Rε亚基敲除的小鼠中，七氟烷对PCs的场电位反应和运动功能的抑制作用减轻。GABAA-Rε亚基被七氟醚激活，导致小脑皮层感觉信息传递受阻，PCs场电位反应和小脑运动功能发育减缓。
结论：本研究为七氟醚在临床麻醉中的安全使用提供了实验依据，提示GABAA-Rε亚单位拮抗剂可考虑与全身麻醉联合应用，预防反复吸入七氟醚在临床上的不良反应。
Fang H, Wang ZH, Bu YJ,etc. Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice.【J】Mol Med Rep. Jan，2018;17(1):1083-1092. doi: 10.3892/mmr.2017.7941.
Background:General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear.
Methods: 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.
Results: 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.
Conclusions: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.
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