2020 年第 11 期 第 15 卷

右美托咪定对颅脑创伤小鼠创伤后应激障碍样行为的影响

Effect of dexmedetomidine on post-traumatic stress disorder-like behavior after traumatic brain injury in mice

作者：张玲张谦安丽娜

英文作者：Zhang Ling Zhang Qian An Lina

单位：中国人民解放军总医院第三医学中心麻醉科，北京100039

英文单位：Department of Anesthesiology the Third Medical Center Chinese PLA General Hospital Beijing 100039 China

关键词：颅脑创伤；右美托咪定；创伤后应激障碍；神经保护

英文关键词：Traumaticbraininjury;Dexmedetomidine;Post-traumaticstressdisorder;Neuroprotection

• 摘要：

• 目的 探讨右美托咪定(Dex)对颅脑创伤小鼠创伤后应激障碍样行为的影响。方法 选取34只成年雄性C57BL/6小鼠按随机数字表法分为3组：假手术组（10只）、颅脑创伤组（12只）、Dex组（12只）。采用液压颅脑撞击致伤仪构建小鼠颅脑创伤模型。伤后Dex组即刻腹腔注射Dex（60 μg/kg，1次/2 h，共3次）。颅脑创伤组仅行颅脑创伤打击，假手术组仅暴露顶骨但不行颅脑创伤打击，此2组均腹腔注射等容积0.9%氯化钠溶液。应用糖水偏爱实验和旷场实验分别检测各组小鼠颅脑创伤前和创伤后第1、3、7天创伤后应激障碍样行为改变，并于颅脑创伤后第7天开始采用Morris水迷宫实验评估各组小鼠学习记忆能力。结果 与假手术组比较，颅脑创伤组小鼠颅脑创伤后第1天糖水偏爱率［（69.4±5.9）%比（84.2±7.1）%］、旷场实验移动距离［（3.4±0.5）m比（5.3±0.3）m］和直立次数［（8.7±1.9）次比（16.9±2.2）次］明显降低/缩短/减少，颅脑创伤后第9天Morris水迷宫实验逃避潜伏期［（36±9）s比（27±6）s］明显延长，颅脑创伤后第11天目标象限穿越平台位置次数［（0.9±0.8）次比（2.3±0.8）次］明显减少（均P＜0.01）。与颅脑创伤组比较，Dex组小鼠颅脑创伤后第3、7天糖水偏爱率［（77.2±4.6）%和（80.2±4.7）%］、移动距离［（4.1±0.4）m和（4.8±0.3）m］和直立次数［（14.1±1.7）次和（16.4±2.3）次］明显增加，颅脑创伤后第9、10天逃避潜伏期［（27±8）s和（23±6）s］明显缩短，颅脑创伤后第11天小鼠目标象限穿越平台位置次数［（1.7±0.9）次］明显增加（P＜0.05或0.01）。结论 右美托咪定可显著改善颅脑创伤小鼠创伤后应激障碍样行为，减轻快感缺乏，促进自主运动和情绪恢复，改善认知功能损伤，发挥神经保护作用。

• Objective To investigate the effect of dexmedetomidine (Dex) on post-traumatic stress disorder（PTSD）-like behavior after traumatic brain injury (TBI) in mice. Methods A total of 34 adult male C57BL/6 mice were randomly divided into the sham operation group(10 mice), TBI group(12 mice), and Dex group(12 mice) . Mice were used to establish the TBI model induced by the fluid percussion impactor for TBI and Dex groups. Dex group was intraperitoneal injected Dex 60 μg/kg immediately (once every 2 h, 3 times) after impacted, and the TBI group were impacted only. Sham operation group  underwent all surgical craniotomy procedure except for the fluid percussion impactor injury, and the groups of sham operation and TBI were intraperitoneal injected by the administration of the same amount of 0.9% sodium chloride injection. The sucrose preference test and open field test were applied to examine the changes of PTSD-like behavior at 1, 3, and 7 d post-TBI, and Morris water maze test was used to evaluate the learning and memory ability of mice at 7 d after TBI. Results Compared with sham operation group, the sucrose preference rate［(69.4±5.9)% vs （84.2±7.1）%］, distance traveled of open field test［(3.4±0.5)m vs （5.3±0.3）m］and vertical numbers  ［(8.7±1.9)times vs （16.9±2.2）times］ in the TBI group were significantly reduced/shortened/reduced at 1 d after TBI, the latency of Morris water maze test［(36±9)s vs （27±6）s］increased at 7 d after TBI, and the times of crossing platform position in target quadrant［(0.9±0.8)times vs （2.3±0.8）times］ reduced at 11 d after TBI(all P＜0.01). Compared with TBI group, sucrose preference rate［(77.2±4.6)%, (80.2±4.7)%］, distance traveled ［(4.1±0.4)m, (4.8±0.3)m］, vertical numbers ［(14.1±1.7)times, (16.4±2.3)times］ were significantly increased at 3 and 7 d, the latency ［(27±8)s, (23±6)s］significantly decreased at 9 and 10 d, and the times of crossing platform position in target quadrant［(1.7±0.9)times］ increased at 11 d after TBI in Dex group (P＜0.05 or 0.01). ConclusionDex exhibited neuroprotective effect in TBI mice through improving PTSD-like behavioral outcome, attenuating anhedonia and cognitive dysfunction, and promoting voluntary movement and emotional recovery.