Chen Ben-Zhen, Jiang Li-Hua, Zhou Wenqin, Shang Yu-Chao, Li Fang, Liu Bin
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Department of Anesthesiology, Sichuan Provincial Women's and Children's Hospital, Chengdu, People's Republic of China.
J Pain Res. 2022 Oct 12;15:3171-3178. doi: 10.2147/JPR.S365253. eCollection 2022.
PURPOSEː: Sevoflurane exposure in the neonatal period of rodent animals was reported to be associated with neuroendocrine dysregulations later in life. We tested the hypothesis that repeated sevoflurane exposure in neonatal rats enhances the sensitivity to pain and acute traumatic stress response later in juvenile life and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAR) activity is involved in mediating these abnormalities.
METHODSː: The postnatal 6 days (P6) Sprague-Dawley male rat pups pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 2.1% sevoflurane exposure for 2 hours daily in 3 consecutive days.
RESULTSː: The results showed that repeated exposures to sevoflurane in neonatal rats significantly reduced the paw withdrawal thermal latency (PWTL) at P9, P45. Repeated exposures to sevoflurane in neonatal rats did not significantly affect the basal secretion of serum corticosterone at juvenile period P45, whereas the level of corticosterone for neonatal sevoflurane-exposed rats at P45 was significantly higher than the CON group after subject to conditioned fear traumatic stress (CFTS). The resulting mRNA ratio was significantly increased immediately after the neonatal rats received the last sevoflurane exposure, which was alleviated by pretreated with the NKCC1 inhibitor bumetanide.
CONCLUSIONː: Repeated exposures to sevoflurane in neonatal rats enhanced the sensitivity to pain and acute traumatic stress response in juvenile life. The neonatal brain depolarizing GABAR activity is involved in mediating these abnormalities.
据报道，啮齿动物在新生期接触七氟醚与生命后期的神经内分泌失调有关。我们测试了这样一个假设，即新生大鼠反复接触七氟醚会增强其在幼年后期对疼痛和急性创伤应激反应的敏感性，并研究新生脑去极化γ-氨基丁酸A型受体（GABAR）活性是否参与介导这些异常。
出生后6天（P6）的雄性Sprague-Dawley幼鼠，预先用溶剂或NKCC1抑制剂布美他尼处理，连续3天每天接受2.1%七氟醚暴露2小时。
结果表明，新生大鼠反复接触七氟醚显著缩短了P9、P45时的爪部撤离热潜伏期（PWTL）。新生大鼠反复接触七氟醚对幼年时期P45时血清皮质酮的基础分泌没有显著影响，而在遭受条件性恐惧创伤应激（CFTS）后，新生期接触七氟醚的大鼠在P45时的皮质酮水平显著高于对照组。新生大鼠接受最后一次七氟醚暴露后，所得的mRNA比值立即显著增加，而用NKCC1抑制剂布美他尼预处理可使其减轻。
新生大鼠反复接触七氟醚会增强其在幼年后期对疼痛和急性创伤应激反应的敏感性。新生脑去极化GABAR活性参与介导这些异常。
