氯胺酮对幼年小鼠空间学习记忆功能及海马脑区TSPO蛋白的影响

Effects of ketamine on the learning and memory ability as well as the TSPO protein expression in hippocampus in juvenile mice

目的：观察幼年小鼠连续多次接受氯胺酮麻醉后学习记忆认知功能及海马脑区内 TSPO 蛋白的表达情况。方法出生21 d 的幼年小鼠24只随机分为对照组（n ＝12）和氯胺酮组（n ＝12），每天1次分别经腹腔注射生理盐水和氯胺酮，连续7 d。然后进行 Morris 水迷宫实验，包括4 d 的适应性训练和1 d 的空间探索实验，观察小鼠的学习记忆功能的改变。水迷宫行为学测试后处死小鼠，取双侧的海马脑区，采用 Western blotting 技术和免疫荧光双标技术检测小鼠海马内小胶质细胞的变化和 TSPO 表达水平。结果训练期3～4 d，氯胺酮组小鼠潜伏期明显长于对照组（P ＜0．05）。探索实验显示，与对照组比较，氯胺酮组小鼠在平台所在象限滞留时间和经过次数明显减少（P ＜0．05）；Western blotting 分析结果表明，氯胺酮组幼年小鼠海马小胶质细胞标记物 Iba-1和 TSPO 蛋白表达明显增多；免疫荧光双重标记技术显示，氯胺酮组小鼠海马小胶质细胞发生了形态学的改变，TSPO 蛋白的表达增强。结论氯胺酮组小鼠海马脑区内小胶质细胞被激活，与之共同表达的 TSPO 蛋白的表达增高，学习记忆等认知功能减退。

Objective To observe the effects of ketamine administered repeatedly on the ability of learning and memory as well as the expression of TSPO protein in hippocampus in juvenile mice.Methods A total of 24 juvenile Wistar mice,aged 21 days,were randomly divided into the control group （n =12）,which received intraperitoneal injection of NS,and the ketamine group （n =12）,which received intraperitoneal injection of ketamine,1 time a day for 7 consecu-tive days.To observe the learning and memory function of mice,Morris water maze was performed in both groups,in-cluding 4-day trail and 1-day probe.After behavior test,the morphological changes and number of the microglia cells and the level of TSPO protein in the bilateral hippocampus tissues were observed using double immunofluorescence standard technique and Western blotting.Results From trail day 3-4,latencies of mice in the ketamine group were sig-nificantly longer than those in the control group （P 〈0.01）.On the probe day,time and frequency during platform quadrant in the ketamine group were significantly shorter than those in the control group （P 〈0.01）.In hippocampus area,Western blotting showed that microglia and TSPO proteins increased;immunofluorescence showed morphological changes in the microglia and higher expression of TSPO protein in the ketamine group.Conclusion Ketamine anesthe-sia reduces not only learning ability but also spatial memory in mice.The microglia cells of hippocampus are activated and TSPO protein is increased.