异氟醚对阿尔茨海默病APPswe/PS1dE9双转基因型小鼠学习记忆能力的影响

Influences of Isoflurane on learning and memory of APPswe/PS1AE9 double transgenic mice of Alzheimer disease

目的研究异氟醚对阿尔茨海默病APPswe/PS1dE9双转基因型小鼠学习记忆能力的影响。方法将转基因小鼠分为转基因异氟醚组(Tg-iso组)及转基因空白对照组(Tg-con组),野生型分为野生异氟醚组(Wt-iso组)及野生空白对照组(Wt-con组)。Tg-iso组及Wt-iso组于7个月龄行异氟醚麻醉,吸入1.1%异氟醚2 h,连续5d。同时Tg-con及Wt-con组吸入30%氧气与70%氮气的混合气体。麻醉后48h各组行水迷宫实验,麻醉后5个月各组行Y迷宫实验。结果 7个月龄时:与Wt-con组比较,Wt-iso组的潜伏期缩短(P=0.013);与Tg-con组比较,Tg-iso组的潜伏期缩短(P=0.043);各组间空间探索实验目标象限时间和路程百分比的差异无统计学意义(P=0.392和P=0.300)。12个月龄时:与Tg-con组比较,Wt-con组和Tg-iso组辨别错误次数明显减少(P=0.044和P=0.020)。结论短时间重复吸入低浓度的异氟醚不增加阿尔茨海默病APPswe/PS1dE9双转基因型小鼠及野生对照型小鼠近期及远期学习记忆能力障碍的风险,反而在一定程度上有减轻的作用。

Objective To study the influences of Isoflurane on learning and memory of APPswe/PS1AE9 double transgenic mice of Alzheimer disease （AD）. Methods Transgenic mice were divided into Tg-iso group and Tg-con group, wild-type mice were divided into Wt-iso group and Wt-con group. At the age of seven months, the Tg-iso group and the Wt-iso group were exposed to 1.1% Isoflurane for 2 hours per day for 5 days. Meanwhile, the mice in the Tg-con group and the Wt-con group inhaled oxygen/nitrogen （FiO2 = 30%）. Learning and memory abilities were tested 48 hours and 5 months after Isoflurane exposure using the Morris Water Maze and Y maze, respectively. Results At the age of seven months, mean latency in the Wt-iso group decreased in a place navigation test compared to the Wt-con group （P = 0.013）; compared to the Tg-con group, the mean latency decreased in the Tg- iso group （P = 0.043）; there was no significant statistical difference in the target quadrant time or distance percentage in probe trials among the groups （P = 0.392）. At the age of twelve months, compared to the Tg-con group, the discrimination errors of the Wt-con and Tg-iso groups decreased （P = 0.044 and 0.020）. Conclusions Repeated low-dose Isoflurane anaesthesia does not increase the dysfunction of learning and memory of APPswe/PS1AE9 double transgenic mice and wild type mice, to some extent, can even decrease dysfunction of learning and memory in APPswe/PS1AE9 double transgenic mice and wild type mice.