七氟醚可影响前额皮质兴奋性神经元的功能性连接蛋白表达而降低老年大鼠记忆能力
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Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal cortex during working memory performance of aged rats
背景与目的
七氟醚会增加老年痴呆症相关的细胞凋亡病理标记物，从而引发了人们对其对导致术后认知功能障碍的担忧。本研究的目的是评估七氟醚对大鼠工作记忆的影响，并探讨其与工作记忆表现中前额皮质（PFC）兴奋性神经元之间的功能连接。
方 法
在18月龄和3月龄的雄性SD大鼠的PFC中植入一个多电极阵列，手术恢复后，分别将老年和成年大鼠分别分为七氟醚组和对照组。七氟醚组的大鼠暴露在1个MAC或1.5个MAC的七氟醚中两个小时。在麻醉后的第1、3、7天，通过y-迷宫评价七氟醚麻醉对工作记忆的影响。当大鼠表面为工作记忆的时候，多电极阵列中记录PFC中兴奋性神经元的尖峰序列。分析描述PFC兴奋性神经元之间的功能连通性。
结 果
成年鼠暴露于1.5个MAC七氟醚后的第1天（P<0.01）时，PFC兴奋性神经元之间的工作记忆和功能连接降低。然而，在老年大鼠暴露于1.5个MAC 七氟醚后的第1、3和7（P<0.01）时PFC兴奋性神经元之间的工作记忆和功能连接减少。暴露于1 MAC 七氟醚后第1天（P<0.01），老年大鼠PFC兴奋性神经元之间的工作记忆和功能连接减少，但它对成年老大鼠没有影响。
结 论
七氟醚诱导的工作记忆障碍可能取决于年龄和麻醉的浓度，可能与PFC兴奋性神经元之间的功能连接蛋白表达减少有关。
原始文献摘要
Xinyu Xu , Xin Tian , Guolin Wang ；Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal cortex during working memory performance of aged rats；Biomedicine & Pharmacotherapy 106 (2018) 1258–1266.
Background: Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to evaluate the effects of sevoflurane on working memory of rats and to characterize functional connectivity between excitatory neurons in the prefrontal cortex (PFC) during working memory performance.
Methods: 18-month-old and 3-month-old male SD rats were implanted with a multielectrode array in the PFC. After recovery from the surgery, the aged and adult rats were divided into sevoflurane group and control group, respectively. Rats in sevoflurane group were exposed to 1 minimum alveolar concentration (MAC) or 1.5 MAC sevoflurane for two hours. At day1, 3, and 7 after exposure, the effects of sevoflurane anesthesia on working memory were investigated in the aged and adult rats by using delayed alternation in Y-maze. Spike trains of excitatory neurons in the PFC were recorded with the multielectrode array while rats were undergoing working memory performance. Functional connectivity between PFC excitatory neurons was described by Granger causal connectivity analysis.
Results: In adult rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1 after exposure (P < 0.01). However, in aged rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1, 3, and 7 after exposure (P < 0.01). 1 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons of aged rats at day1 after exposure (P < 0.01), but it had no effect in adult rats.
Conclusions: Sevoflurane-induced working memory impairment may depend on advanced age and anesthetic concentration. These findings also suggest, in rats, that sevoflurane-induced working memory impairment may be related to the decreased functional connectivity between PFC excitatory neurons.
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编辑：王贵龙 审校：李华宇