中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 96-102.doi: 10.4103/1673-5374.264468

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

七氟醚比异氟醚对认知功能损害轻：对恐惧记忆保留作用有限

  


  • 出版日期:2020-01-15 发布日期:2020-05-20
  • 基金资助:

    国家自然科学基金项目（81730033，81701371）

Sevoflurane plays a reduced role in cognitive impairment compared with isoflurane: limited effect on fear memory retention

Ying Du1, Xiang-Dan Gong1, Xin Fang1, Fang Xing1, Tian-Jiao Xia2, Xiao-Ping Gu1   

  1. 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, Jiangsu Province, China

    2 Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu Province, China

  • Online:2020-01-15 Published:2020-05-20
  • Contact: Tian-Jiao Xia, PhD, tjxia@nju.edu.cn; Xiao-Ping Gu, PhD, xiaopinggu@nju.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81730033 (to XPG), No. 81701371 (to TJX).

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摘要：

异氟烷和七氟醚都是吸入麻醉剂，但在临床应用中由于七氟醚存在分解代谢化合物及其潜在的肾毒性，使得异氟醚被认为更适于长期麻醉。但是近来有研究认为2种吸入麻醉剂在肝肾毒性、价格以及长期麻醉效果方面是相似的，且七氟醚可能对年轻小鼠的认知影响更小。为此实验以8-10周龄C57BL/6小鼠为研究对象，分别以1.2％异氟烷或2.4％七氟醚暴露6h，以新颖物体识别、条件化情景恐惧测试以及提示恐惧记忆消退测试分析小鼠认知功能和记忆过程的变化，以Western blot分析小鼠海马中多巴胺D1受体、儿茶酚-O-甲基转移酶、磷酸糖原合成酶激酶3β和总糖原合成酶激酶3β的表达情况。结果发现(1)暴露于七氟醚的小鼠在新颖物体识别中没有明显的受损的表现，且在条件化情景恐惧测试中情境记忆障碍时间比异氟醚更短；(2)长期使用七氟醚不会影响记忆巩固，而异氟醚则会导致记忆巩固和保留能力下降；(3)海马中多巴胺D1受体的下调以及磷酸化糖原合成酶激酶3β磷酸化和儿茶酚-O-甲基转移酶上调，可能与暴露于异氟醚或七氟醚后的不同记忆表现有关；(4)结果提示七氟醚比异氟醚对认知障碍的作用小，其可能与海马中多巴胺D1受体和儿茶酚-O-甲基转移酶表达以及糖原合成酶激酶3β磷酸化有关。实验于2017-11-16经南京大学机构动物伦理委员会批准，批准号20171102。

orcid: 0000-0002-7676-4651 (Tian-Jiao Xia)
         0000-0002-8218-7299 (Xiao-Ping Gu)

关键词:

七氟醚, 异氟醚, 恐惧记忆, 认知障碍, 神经毒理学, 儿茶酚-O-甲基转移酶, 多巴胺D1受体, 糖原合成酶激酶3β, 神经再生

Abstract:

Isoflurane and sevoflurane are both inhalation anesthetics, but in clinical application, sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity. Nevertheless, recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity, cost, and long-term anesthetic effect. Moreover, sevoflurane possibly has less cognitive impact on young mice. In this study, C57BL/6 mice aged 8–10 weeks were exposed to 1.2% isoflurane or 2.4% sevoflurane for 6 hours. Cognitive function and memory were examined in young mice using the novel object recognition, contextual fear conditioning, and cued-fear extinction tests. Western blot assay was performed to detect expression levels of D1 dopamine receptor, catechol-O-methyltransferase, phospho-glycogen synthase kinase-3β, and total glycogen synthase kinase-3β in the hippocampus. Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test. Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group. Long-term sevoflurane exposure did not affect memory consolidation, while isoflurane led to memory consolidation and reduced retention. Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3β and upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane. These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane, which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3β in the hippocampus. This study was approved by the Institutional Animal Care and Use Committee, Nanjing University, China on November 20, 2017 (approval No. 20171102).

Key words: catechol-O-methyltransferase, cognitive impairment, D1 dopamine receptors, fear memory, glycogen synthase kinase-3β, isoflurane, neurotoxicology, sevoflurane