隗闯 张萌 武瑞 王玉亭 王钥 周宇

[摘要] 目的 探讨细胞集落刺激因子1受体（CSF1R）抑制剂PLX5622对C57BL/6小鼠空间型学习与记忆的影响。方法 16只健康雄性C57BL/6小鼠随机分为实验组和对照组，各8只。实验组小鼠连续2周投食含PLX5622的鼠粮，对照组小鼠投食等量的标准鼠粮。采用Morris水迷宫实验检测两组小鼠的空间型学习力与记忆力;应用荧光免疫组化法测定两组小鼠海马区域小胶质细胞的密度。结果 水迷宫结果显示，与对照组相比，实验组小鼠在圆台所在象限探索的时长百分比明显下降（t=3.556，P<0.01），逃避潜伏期、穿越圆台次数、游泳速度差异无显著性（P>0.05）。荧光免疫组化结果显示，与对照组相比，实验组小鼠每平方毫米海马区域小胶质细胞的数量明显减少（t=11.430，P<0.01），成熟神经元数量两组比较差异无显著性（P>0.05）。结论 海马区域小胶质细胞清除不影响小鼠空间学习与记忆获取，但削弱小鼠的空间型记忆力。

[关键词] 小神经胶质细胞;迷宫学习;海马;小鼠

[中图分类号] R338.2  [文献标志码] A  [文章编号] 2096-5532（2020）02-0173-04

doi：10.11712/jms.2096-5532.2020.56.089 [开放科学（资源服务）标识码（OSID）]

[网络出版] http：//kns.cnki.net/kcms/detail/37.1517.R.20200519.1430.004.html;2020-05-20 08：57

[ABSTRACT] Objective To investigate the effect of the colony-stimulating factor 1 receptor inhibitor PLX5622 on the spatial learning and memory in C57BL/6 mice.  Methods A total of 16 healthy male C57BL/6 mice were randomly divided into control group and experimental group， with 8 mice in each group. The mice in the experimental group were given PLX5622-based chow diet for 2 consecutive weeks， and those in the control group were given an equivalent amount of normal chow diet. Morris water maze test was conducted to evaluate the spatial learning and memory of the mice. Fluorescent immunohistochemistry was used to determine the density of microglial cells in the hippocampus of the mice.  Results Morris water maze test showed that the searching time （%） for the platform in the target quadrant was significantly reduced in the experimental group compared with that in the control group （t=3.556，P<0.01）， while the escape latency， number of platform crossings， and swimming speed were not significantly different between the two groups （P>0.05）. Fluorescent immunohistochemistry showed that the number of microglial cells per square millimeter of the hippocampus was significantly reduced in the experimental group compared with that in the control group （t=11.430，P<0.01）， while the number of mature neurons was not significantly different between the two groups （P>0.05）.  Conclusion Microglial cell elimination in the hippocampus has no significant effect on spatial learning and memory acquisition in mice， but it reduces the spatial memory of the mice.

[KEY WORDS] microglia; maze learning; hippocampus; mice

越来越多的实验结果显示，神经炎症和多种神经退变性疾病（如阿尔兹海默症和帕金森病等）的發生相关度很大[1-4]。小胶质细胞是神经并发炎症的一个重要的参与者[5-6]。在健康的情况下，小胶质细胞可以维持大脑的微环境平衡，保护其神经元;中枢神经系统受到损伤或感染时，小胶质细胞发生炎症反应性激活即M1极化，高表达炎性细胞因子，同时细胞形态发生改变，吞噬细胞碎片，利于损伤修复;而过度激活的小胶质细胞则引起促炎性细胞因子大量增加，诱导慢性炎症并导致神经元死亡[7-12]。……