基础医学与临床 ›› 2019, Vol. 39 ›› Issue (4): 478-482.

• 研究论文 • 上一篇    下一篇

APP/PS1双转基因AD小鼠术后认知功能紊乱及其机制

于琳琳,李正迁,韩登阳,杨宁,倪诚,史成梅,郭向阳   

  1. 北京大学第三医院
  • 收稿日期:2018-12-20 修回日期:2019-01-15 出版日期:2019-04-05 发布日期:2019-03-26
  • 通讯作者: 郭向阳 E-mail:puthmzk@163.com
  • 基金资助:
    α-突触核蛋白寡聚化在术后认知功能障碍转归中的作用及分子机制;褪黑素生物节律对异氟醚麻醉后认知功能影响的DNA甲基化机制研究

Postoperative neurocognitive disorders and the potential mechanisms in APP/PS1 double transgenic AD mice

  • Received:2018-12-20 Revised:2019-01-15 Online:2019-04-05 Published:2019-03-26
  • Contact: Xiang-yang GUO E-mail:puthmzk@163.com

摘要: 目的 探究阿尔茨默海病(AD)双转基因小鼠(APP/PS1)在麻醉手术后不同时程的认知功能改变及其可能的机制。方法 将APP/PS1小鼠随机分为对照组(不予手术麻醉干预)和实验组(2.5%七氟烷麻醉下行剖腹探查术)。术后1和3 d行条件恐惧实验评估小鼠认知功能;并分别在术后12及24 h和3 d用酶联免疫吸附实验检测海马组织炎性因子IL-6、IL-1β、TNF-α及淀粉样蛋白Aβ42蛋白含量;用Western blot检测α-突触核蛋白的表达。结果 与对照组相比,实验组小鼠在术后1和3 d,与场景有关的僵直时间均显著减少。术后24 h实验组小鼠海马组织内IL-1β、IL-6及TNF-α的含量显著高于对照组(P<0.05);同时Aβ42蛋白和α-突触核蛋白的表达在术后24 h也显著上调(P<0.05)。结论 AD双转基因小鼠接受麻醉手术后,在术后早期即可出现认知功能障碍,其发生机制可能与海马区α-突触核蛋白与Aβ42表达异常及神经炎性反应相关。

关键词: APP/PS1转基因小鼠, 术后神经认知功能改变, α-突触核蛋白

Abstract: Objective To study neurocognitive changes at different postoperative time points and the potential mechanisms in APP/PS1 transgenic mice (2xTg AD mice). Methods APP/PS1 mice were randomly divided into two groups, experiment group (received laparotomy under 2.5% sevoflurane anesthesia) and control group. Fear conditioning test was introduced to assess the cognitive function at 1d and 3ds after the anesthesia/surgery. The content of alpha-synuclein in hippocampus was determined by Western blot, while the contents of Aβ42, IL-6, IL-1beta, and TNF-alpha were quantified by ELISA kits at different postoperative time points (12h, 24h and 3d). Results Compared with the control group,the context-associated freezing duration was significantly decreased at 1d and 3ds after the Anesthesia/surgery; the concentration of IL-6,IL-1beta and TNF-alpha significantly increased at 24hs after the Anesthesia/surgery; the content of alpha-synuclein and Aβ42 also significantly increased at 24hs after the Anesthesia/surgery(P<0.05). Conclusion The anesthesia/surgery has effects on the short-term cognitive function of 2xTgAD mice. The potential mechanisms may be associated with the variation of alpha-synuclein and amyloid-β42, besides neuroinflammation.

Key words: APP/PS1 transgenic mice, postoperative neurocognitive disorders, alpha-synuclein

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