海藻糖对异氟烷诱导转APP基因小鼠学习记忆功能的影响

Effects of trehalose on learning and memory impairment induced by isoflurane in APP transgenic mice

目的探讨吸入麻醉药异氟烷对转APP基因小鼠学习记忆功能的影响及海藻糖的干预保护作用。方法 60只12月龄转APP小鼠随机分为空白对照组(Control组)、异氟烷组(Iso组)、海藻糖组(Iso+Tre组),每组20只。Iso+Tre组和Iso组分别于麻醉前30 min腹腔注射海藻糖400μg/kg或等量生理盐水,然后给予1.4%异氟烷吸入麻醉2 h,麻醉后24 h应用Morris水迷宫测试小鼠学习记忆能力,麻醉后6、24 h杀鼠取脑,采用TUNEL染色观察各组小鼠海马区神经元凋亡,应用ELISA法检测Aβ含量,Western印迹法检测Bcl-2、Bax、Caspase-3的表达变化。结果与Control组相比,Iso组小鼠总体的平均逃避潜伏期明显延长,空间探索时间明显缩短(P<0.01),海马神经元凋亡指数、Aβ含量、Bax/Bcl-2比值及Caspase-3表达均明显增加(P<0.01);Iso+Tre组与Iso组相比,逃避潜伏期缩短,空间探索时间延长(P<0.05),Aβ含量、Bax/Bcl-2比值及Caspase-3表达均明显减少(P<0.01)。结论海藻糖能够改善异氟烷诱导转APP基因小鼠学习记忆能力的损害,减少海马神经元的凋亡及Aβ的生成。

Objective To observe the influence of inhalation anesthestic isoflurane on the learning-memory ability of APP transgenic mice and protective effects of trehalose. Methods 60 APP transgenic mice at the age of 12 months were divided into control,Iso and Iso+Tre groups. The abilities of learning and memory were investigated by Morris water maze. TUNEL assay was employed to observe the hippocampal neuron apoptosis of the mice in each group. The amount of Aβ was checked by ELISA assay kit and the variations of Bcl-2,Bax,Caspase-3 were examined by Western blot. Results In comparison with those of control group,the mean escape latency of Iso group was prolonged,the spatial exploring time was reduced,apoptotic index,the amount of Aβ,the ratio of Bax / Bcl-2,and the expression of Caspase-3 were increased. Moreover,compared to those of Iso group,escape latency of Iso+Tre was shorter,longer spatial exploring time was longer,the amount of Aβ,ratio of Bax / Bcl-2,and Caspase-3 expression were lower. Conclusions Trehalose could improve the recovery of the learning and memory of APP transgenic mice after isoflurane anesthesia,the hippocampal neuron apoptosis and the production of Aβcan be inhibited by trehalose.