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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (4): 55-60.doi: 10.6040/j.issn.1671-7554.0.2014.584

• 基础医学 • 上一篇    下一篇

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

李桂婷1, 张蕊1, 邹珊珊1, 丁明2   

  1. 1. 潍坊医学院麻醉学系, 山东 潍坊 261053;
    2. 解放军第八十九医院麻醉科, 山东 潍坊 261021
  • 收稿日期:2014-09-07 修回日期:2015-03-09 出版日期:2015-04-10 发布日期:2015-04-10
  • 通讯作者: 张蕊.E-mail:zhangrui@wfmc.edu.cn E-mail:zhangrui@wfmc.edu.cn
  • 基金资助:
    山东省教育厅课题(J13LL02)

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

LI Guiting1, ZHANG Rui1, ZOU Shanshan1, DING Ming2   

  1. 1. Department of Anesthesiology, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Anesthesiology, the 89th Hospital of PLA, Weifang 261021, Shandong, China
  • Received:2014-09-07 Revised:2015-03-09 Online:2015-04-10 Published:2015-04-10

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摘要： 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.

关键词: 学习记忆能力, 小胶质细胞, 氯胺酮, 18 kDa转位蛋白

Abstract: 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 consecutive days. To observe the learning and memory function of mice, Morris water maze was performed in both groups, including 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 significantly 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 anesthesia reduces not only learning ability but also spatial memory in mice. The microglia cells of hippocampus are activated and TSPO protein is increased.

Key words: Ketamine, Microglia cell, Learning and memory ability, 18 kDa translocator protein

中图分类号: 

  • R971
[1] Eghbal MH, Taregh S, Amin A, et al. Ketamine improves postoperative pain and emergence agitation following adenotonsillectomy in children. A randomized clinical trial[J]. Middle East J Anesthesiol, 2013, 22(2): 155-160.
[2] 蒯建科, 孙绪德, 高昌俊, 等. 氯胺酮对新生大鼠认知功能和海马突触素表达的影响[J]. 医学研究生学报, 2008, 21(4): 364-367. KUAI Jianke, SUN Xude, GAO Changjun, et al. Effects of ketamine on the cognitive function and hippocampus synaptophysin expression in neonatal rats[J]. Journal of Medical Postgraduates, 2008, 21(4): 364-367.
[3] Bae KR, Shim HJ, Balu D, et al. Translocator protein 18 kDa negatively regulates inflammation in microglia[J]. J Neuroimmune Pharmacol, 2014, 9(3): 424-437.
[4] 赵悦, 左萍萍, 郎森阳. TSPO: 外周苯二氮受体的新命名及其在中枢神经系统中的作用[J]. 中国药理学通报, 2010, 26(4): 432-435. ZHAO Yue, ZUO Pingping, LANG Senyang. TSPO: new nomenclature for the peripheral benzodiazepine receptor and its role in the neuropsycopharmacology[J]. Chinese Pharmacological Bulletin, 2010, 26(4): 432-435.
[5] Zhou X, He B, Zhu Z, et al. Etifoxine provides benefits in nerve repair with acellular nerve grafts[J]. Muscle Nerve, 2014, 50(2): 235-243.
[6] Da Settimo F, Simorini F, Taliani S, et al. Anxiolytic-like effects of N, N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis[J]. J Med Chem, 2008, 51(18): 5798-5806.
[7] Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children[J]. AnesthAnalog, 2007, 104(7): 509-520.
[8] Ribeiro PO, Tomé AR, Silva HB, et al. Clinically relevant concentrations of ketamine mainly affect long-term potentiation rather than basal excitatory synaptic transmission and do not change paired-pulse facilitation in mouse hippocampal slices[J]. Brain Res, 2014, 1560: 10-17.
[9] Hayashi Y, Nakanishi H. Synaptic plasticity and synaptic reorganization regulated by microglia[J]. Nihon Shinkei Seishin Yakurigaku Zasshi, 2013, 33(5-6): 211-216.
[10] 王志萍, 武云飞, 江山, 等. 多次氯胺酮给药对大鼠海马 CA1 区突触长时程增强的影响[J]. 中华麻醉学杂志, 2006, 6(4): 309-311. WANG Zhiping, WU Yunfei, JIANG Shan, et al. The effect of repeated ketamine administration on long-term potential in area CA1 of hippocampus in rats[J]. Chinese Journal of Anesthesiology, 2006, 26(4): 309-311.
[11] Sparkman NL, Buchanan JB, Heyen JR, et al. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers[J]. J Neurosci, 2006, 26(42): 10709-10716.
[12] D'Agostino G1, Kim JD, Liu ZW et al. Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory[J]. Cereb Cortex, 2013, 23(8): 2007-2014.
[13] Wei XH, Wei X, Chen FY, et al. The up regulation of translocator protein (18 kDa) promotes recovery from neuropathic pain in rats[J]. J Neurosci, 2013, 33(4): 1540-1551.
[14] Mills C, Makwana M, Wallace A, et al. RO5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats[J]. Eur J Neurosci, 2008, 27(4): 937-946.
[15] 宿明艳, 钱燕宁, Toll样受体4在小胶质细胞炎症反应中的作用与认知功能的关系[J]. 国际麻醉学与复苏杂志, 2013, 34(9): 840-842, 864. SU Mingyan, QIAN Yanning. The role of toll-like receptor 4 in the inflammatory response of the microglia and the relationship with cognitive function[J]. Int J Anesth Resus, 2013, 34(9): 840-842, 864.
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