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目的:探讨艾司氯胺酮对颅脑创伤后应激障碍(PTSD)行为的影响。方法:选取36只成年雄性SD大鼠按随机数字表法分为3组，采用皮质撞击致伤法构建小鼠颅脑创伤模型，假手术组(Sham组，n n＝12)仅打开骨窗不行颅脑创伤打击，颅脑创伤组(TBI组，n n＝12)和艾司氯胺酮处理组(TBI+ES组，n n＝12)行皮质打击；创伤后TBI+ES组即刻腹腔注射艾司氯胺酮(10 mg/kg，1次/2 h，共3次)，TBI组和Sham组腹腔注射等容积0.9%氯化钠溶液。收集创伤后第(1、3、7、15)天进行糖水偏爱实验、第16天开始旷场实验、第17天开始高架十字迷宫实验结果，分析颅脑创伤后PTSD样行为改变，并于颅脑创伤后第18~23天开始采用Morris水迷宫实验评估各组大鼠学习记忆能力。实验结束后大鼠安乐死取脑组织，Western-blot分析脑源性神经营养因子(BDNF)和突触后致密蛋白95(PSD95)、突触素表达水平。正态分布的计量资料以均数±标准差(n ±n s)表示，多组间比较用单因素方差分析(One-Way ANOVA)，两两比较采用SNK-n q检验，重复测量资料采用LSD法。n 结果:TBI组大鼠糖水偏爱率、移动格数、直立次数、开臂停留时间、开臂进入次数、逃避潜伏期和穿越平台位置次数[分别为(75.8±4.9)%、(30.9±4.1)格、(12.4±2.6)次、(40.3±8.5) s、(6.8±2.3)次、(30.0±4.6) s、(7.0±2.5)次]、低于Sham组[分别为(85.3±4.4)%、(40.5±5.4)格、(17.3±2.7)次、(95.8±12.4) s、(15.3±3.1)次、(18.3±7.8) s、(15.7±2.6)次]，差异具有统计学意义(n P<0.05)；TBI+ES组糖水偏爱率、移动格数、直立次数、开臂停留时间、开臂进入次数、逃避潜伏期和穿越平台位置次数[分别为(82.9±5.5)%、(35.5±5.5)格、(15.1±2.4)次、(68.4±9.7) s、(12.1±3.2)次、(22.3±8.8) s、(12.5±4.1)次]高于TBI组，差异具有统计学意义(n P<0.05)。TBI+ES组BDNF、PSD95和突触素表达水平[分别为(0.43±0.08)、(0.22±0.02)、(0.31±0.04)]高于TBI组[分别为(0.19±0.02)、(0.20±0.02)、(0.24±0.01)]，差异具有统计学意义(n P<0.05)，且均低于Sham组[分别为(0.89±0.11)、(0.45±0.12)、(0.57±0.15)]，差异具有统计学意义(n P<0.05)。n 结论:艾司氯胺酮显著减少颅脑创伤大鼠PTSD样行为，发挥神经保护作用，可能作为PTSD治疗的潜在药物。“,”Objective:To investigate the effects of esketamine on the behavior of post-traumatic stress disorder(PTSD).Methods:Thirty-six adult male SD rats were randomly divided into three groups. The mouse craniocerebral trauma model was established by cortical impact injury method. The Sham group (n n=12) only opened the bone window without craniocerebral trauma. The TBI group(n n=12) and the TBI+ ES group(n n=12) were subjected to cortical trauma; Immediately after trauma, the TBI+ ES group was intraperitoneally injected with esmketamine (10 mg/kg, once every two hours, three times in total), and the TBI group and Sham group were intraperitoneally injected with equal volume 0.9% sodium chloride solution. The results of sugar water preference test, open field test on day 16 and elevated cross maze test on day 17 were collected to analyze PTSD like behavior changes, and Morris water maze test was used to evaluate the learning and memory ability of rats in each group from day 18 to 23 after craniocerebral trauma. After the experiment, the rats were euthanized and the brain tissues were taken. The expression levels of brain-derived neurotrophic factor (BDNF), synaptic protein PSD95 and synaptophysin (Syp) were analyzed by Western blot. The measurement data of normal distribution were expressed as mean ± standard deviation (n ±n s). One way ANOVA was used for multi group comparison, SNK-n q test was used for post pairwise comparison, and LSD method was used for repeated measurement data.n Results:In the TBI group, the preference rate of sugar water, the number of moving grids, the number of standing upright, the residence time of open arm, the number of open arm entry, the escape latency and the number of crossing platform [(75.8±4.9)%, (30.9±4.1) grids, (12.4±2.6) times, (40.3±8.5) s, (6.8±2.3) times, (30.0±4.6) s and (7.0±2.5) times] were significantly lower than Sham group [(85.3±4.4)%, (40.5±5.4) grid, (17.3±2.7) times, (95.8±12.4) s, (15.3±3.1) times, (18.3±7.8) s, (15.7±2.6) times] (n P< 0.05); In TBI+ ES group, the sugar water preference rate, the number of moving grids, the number of upright times, the time of open arm stay, the number of open arm entry, the number of escape latency and the number of crossing platform position [(82.9±5.5)%, (35.5±5.5) grids, (15.1±2.4) times, (68.4±9.7) s, (12.1±3.2) times, (22.3±8.8) s and (12.5±4.1) times] were significantly higher than those in TBI group (n P<0.05). The expression levels of BDNF, PSD95 and Syp in TBI+ ES Group [0.43±0.08), (0.22±0.02), (0.31±0.04)] were higher than those in TBI group [0.19±0.02), (0.20±0.02), (0.24±0.01)], the difference was significant (n P<0.05), and they were lower than those in Sham group [0.89±0.11), (0.45±0.12), (0.57±0.15)], and the difference was significant (n P<0.05).n Conclusion:Esticketamine significantly reduce PTSD-like behavior in TBI rats and play a neuroprotective role, which may be a potential medicinefor PTSD treatment.