APP/PS1双转基因AD小鼠术后认知功能紊乱及其机制

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

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Aβ_(42)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Aβ_(42)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Aβ_(42)表达异常及神经炎性反应相关。

Objective To study neurocognitive changes at different postoperative time points and the potential mechanisms in APP/PS1 transgenic mice(2 xTg 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 day 1 and day 3 after the anesthesia/surgery. The content of alpha-synuclein in hippocampus was determined by Western blot, while the contents of Aβ42, IL-6, IL-1 beta, and TNF-alpha were quantified by ELISA kits at different postoperative time points(12 h, 24 h and 3 d). Results Compared with the control group,the context-associated freezing duration was significantly decreased at day 1 and day 3 after the anesthesia/surgery;the concentration of IL-6,IL-1 beta and TNF-alpha significantly increased 24 hours after anesthesia/surgery;the content of alpha-synuclein and Aβ42 also significantly increased 24 hours after the anesthesia/surgery(P<0.05). Conclusions The anesthesia/surgery has positive effects on the short-term cognitive function of 2 xTg AD mice. The potential mechanisms may be associated with the variation of alpha-synuclein and amyloid-β42, besides neuroinflammation.