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中华神经创伤外科电子杂志

中华神经创伤外科电子杂志 ›› 2021, Vol. 07 ›› Issue (02) : 68 -74. doi: 10.3877/cma.j.issn.2095-9141.2021.02.002

所属专题： 文献；

颅脑创伤

氢水对小鼠闭合性轻型颅脑损伤后焦虑抑郁样行为的改善作用探讨
卢盛华1, 徐晓健1, 王学蛟2, 高飞1, 张斌1, 葛芊芊1, 杨梦石1, 牛非1, 董金千1, 庄园1, 刘佰运1, 田润发1,†()   
  1. 1. 100070　北京市神经外科研究所中枢神经系统损伤研究北京市重点实验室和首都医科大学附属北京天坛医院神经外科
    2. 037008　大同市第三人民医院神经外科
  • 收稿日期:2021-01-19 出版日期:2021-04-15
  • 通信作者: 田润发
  • 基金资助:
    国家自然科学基金(81801225，81771328)

Ameliorative effect of hydrogen water on mice with anxiety and depression-like behavior after repetitive mild brain injury

Shenghua Lu1, Xiaojian Xu1, Xuejiao Wang2, Fei Gao1, Bin Zhang1, Qianqian Ge1, Mengshi Yang1, Fei Niu1, Jinqian Dong1, Yuan Zhuang1, Baiyun Liu1, Runfa Tian1,†()   

  1. 1. Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
    2. Department of Neurosurgery, Third People’s Hospital of Datong, Datong 037008, China
  • Received:2021-01-19 Published:2021-04-15
  • Corresponding author: Runfa Tian
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引用本文：

卢盛华, 徐晓健, 王学蛟, 高飞, 张斌, 葛芊芊, 杨梦石, 牛非, 董金千, 庄园, 刘佰运, 田润发. 氢水对小鼠闭合性轻型颅脑损伤后焦虑抑郁样行为的改善作用探讨[J]. 中华神经创伤外科电子杂志, 2021, 07(02): 68-74.

Shenghua Lu, Xiaojian Xu, Xuejiao Wang, Fei Gao, Bin Zhang, Qianqian Ge, Mengshi Yang, Fei Niu, Jinqian Dong, Yuan Zhuang, Baiyun Liu, Runfa Tian. Ameliorative effect of hydrogen water on mice with anxiety and depression-like behavior after repetitive mild brain injury[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2021, 07(02): 68-74.

目的

建立并验证闭合性反复轻型颅脑损伤(rmTBI)动物模型，探讨氢水对rmTBI模型动物的神经保护作用及其导致的行为学结果差异。

方法

选用C57BL/6小鼠20只，随机分为对照组（4只）、打击组（8只）和干预组（8只），打击组和干预组使用闭合性颅脑打击装置，打击1次/d，连续5 d。对照组和打击组使用纯净水喂养，干预组使用氢水（H2含量0.003‰）喂养，打击后1、3、5、7、15、30 d应用旷场实验、高架十字平台迷宫实验和悬尾实验评价小鼠焦虑抑郁样行为。

结果

末次打击后3 d，对照组小鼠悬尾实验静止潜伏期显著长于打击组（P<0.05），探索高架十字迷宫开臂时间显著长于打击组（P<0.05），而与干预组均无显著差异（P>0.05）；打击后15 d，旷场实验中对照组静止时间显著短于打击组与干预组（P<0.05），攀壁次数显著多于打击组与干预组（P<0.05），而打击组与干预组间差异无统计学意义（P>0.05）。打击后30 d，对照组小鼠高架十字平台迷宫探索开臂时间显著长于打击组及干预组（P<0.05），而打击组与干预组间差异无统计学意义（P>0.05）。

结论

氢水对rmTBI小鼠伤后早期易激惹、活动减少等症状有一定改善作用，但对预防和治疗伤后中远期的抑郁样行为及学习探索能力障碍无效。

关键词: 反复轻型颅脑损伤, 脑震荡, 脑震荡后综合征, 慢性创伤性脑病, 实验装置设计, 动物行为学实验
Objective

To establish and verify the animal model of repetitive mild traumatic brain injury (rmTBI), and to verify the protective effect of hydrogen water on rmTBI model animals and the behavioral improvement caused by hydrogen water.

Methods

Twenty C57BL/6 mice were randomly divided into control group (n=4), impact group (n=8) and intervention group (n=8). The impact group and intervention group were treated with closed craniocerebral percussion device once a day for 5 consecutive days. The control group and the impact group were fed with pure water, and the intervention group were fed with hydrogen water (H2 content 0.003‰). The open-field test, elevated plus-maze and tail suspension test were used to evaluate the anxiety and depression-like behavior of mice on the 1st, 3rd, 5th, 7th, 15th, 30th day-post impact (DPI).

Results

On DPI 3, the resting latency of the suspended tail test in the control was significantly longer than that in the impact group (P<0.05), whereas it was not significantly different from that in the intervention group; on DPI 3, the open-arm exploring time of elevated plus-mazae by the control group was significantly longer than that of the impact group (P<0.05), whereas it was not significantly different from that of the intervention group; on DPI 15, the resting time of the control group in the open-field test was significantly shorter than that of the intervention group (P<0.05), and the number of wall climbing was significantly greater than that of the intervention group (P<0.05), whereas there was no significant difference between the impact group and the intervention group. On DPI 30, the open arm time of the elevated plus-maze exploration in the control mice was significantly longer than that in the impact and intervention groups (P<0.05), whereas there was no statistical difference between the impact and intervention groups.

Conclusion

Hydrogen water showed some ameliorative effects on symptoms such as irritability and reduced activity in the early stage after injury in rmTBI mice, but it was not effective in preventing and treating depression-like behaviors and exploratory memory impairment in long term observation after injury.

Key words: Repetitive mild traumatic brain injury, Brain concussion, Post-concussion syndrome, Chronic traumatic encephalopathy, Equipment design, Animal behavior test
图1 实验总体流程
表1 轻型颅脑损伤评分
评价项目 得分
一过性呼吸暂停时间（s）  
  <2 0
  2~15 1
  >15 2
一过性反射消失时间（s）  
  <5 0
  5~20 1
  >20 0
意识恢复后无运动障碍和反射异常  
  无 1
  有 2
肉眼可见外观畸形  
  无 0
  有 4
表2 打击效果观察
组别 只数 死亡数量 打击较轻（次） 效果理想（次） 打击过重（次） 总次数
打击组 8 0 5 33 2 40
干预组 8 1 7 26 4 37
图2 3组小鼠旷场实验表现
图3 3组小鼠高架十字平台行为学结果
图4 3组小鼠悬尾实验表现
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