维生素C在急性大剂量乙醇摄入后颅脑损伤中作用的研究

doi:10.3877/cma.j.issn.2095-9141.2020.02.009

中华神经创伤外科电子杂志 ›› 2020, Vol. 06 ›› Issue (02) : 105 -109. doi: 10.3877/cma.j.issn.2095-9141.2020.02.009

所属专题：文献；

基础研究

维生素C在急性大剂量乙醇摄入后颅脑损伤中作用的研究

伍宵¹, 高飞², 董金千², 茆翔³^,^†(

), 刘佰运⁴

^1. 230022　合肥，安徽医科大学第一附属医院急诊科
^2. 100070　北京，首都医科大学附属北京天坛医院神经外科
^3. 230022　合肥，安徽医科大学第一附属医院神经外科
^4. 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

收稿日期:2020-02-10 出版日期:2020-04-15
通信作者: 茆翔
基金资助:
国家自然科学基金(81171144，81471238); 国家自然科学基金培育基金(2016KJ12); 北京市卫生健康委员会2020年预算项目(PXM2020_026280_000002)

Effect of vitamin C for the pre-injury high ethanol intake in rats following traumatic brain injury

Xiao Wu¹, Fei Gao², Jinqian Dong², Xiang Mao³^,^†(), Baiyun Liu⁴

^1. Department of Emergency, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
^2. Department of Neurosurgery, Capital Medical University, Beijing 100070, China
^3. Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
^4. 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

Received:2020-02-10 Published:2020-04-15
Corresponding author: Xiang Mao
About author:
Corresponding author: Mao Xiang, Email: xiangmao1002@163.com

全文 ( ) 下载PDF ( ) 导出引用

引用本文：

伍宵, 高飞, 董金千, 茆翔, 刘佰运. 维生素C在急性大剂量乙醇摄入后颅脑损伤中作用的研究[J/OL]. 中华神经创伤外科电子杂志, 2020, 06(02): 105-109.

Xiao Wu, Fei Gao, Jinqian Dong, Xiang Mao, Baiyun Liu. Effect of vitamin C for the pre-injury high ethanol intake in rats following traumatic brain injury[J/OL]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2020, 06(02): 105-109.

目的

探讨维生素C（VitC）在急性大剂量乙醇摄入后颅脑损伤（TBI）后继发性脑损伤的作用及其可能机制。

方法

将实验大鼠随机分为打击+生理盐水组（TBI+only）；打击+乙醇+生理盐水组（TBI+EtOH）；打击+VitC组（TBI+VitC）；打击+乙醇+VitC组（TBI+EtOH+VitC），每组10只。建立中度TBI模型，TBI后24 h进行神经功能损伤评分、脑含水量及伊文氏蓝含量测定；采用Western blot法测定TBI后24 h的损伤侧脑组织中细胞色素P450（CYP2E1），水通道蛋白-4（AQP-4），基质金属蛋白酶-9（MMP-9）和血脑屏障紧密连结蛋白（Occludin）的表达情况。

结果

打击24 h后，TBI+EtOH组的神经功能损伤评分、脑含水量和伊文氏蓝含量明显增加，VitC干预后，各项指标明显减少，组间差异有统计学意义（P<0.05）；与TBI+EtOH组相比，TBI+EtOH+VitC组的CYP2E1表达减少，AQP-4和MMP-9的含量降低，Occludin的含量增高，组间差异有统计学意义（P<0.05）。

结论

急性乙醇摄入加剧了TBI后细胞毒性脑水肿，而VitC可通过CYP2E1减少AQP-4和MMP-9的激活，增加Occludin蛋白的表达，减少血脑屏障紧密连接的分解及完整性的破坏，降低血脑屏障的开放并减轻脑水肿，最终改善神经功能。

关键词: 乙醇摄入, 颅脑损伤, 维生素C, CYP2E1

Objective

To investigate the effect of vitamin C (VitC) on reducing secondary brain injury caused by traumatic brain injury (TBI) after alcohol consumption and its possible mechanism.

Methods

Rats were randomly assigned into TBI+only group, TBI+EtOH group, TBI+VitC group and TBI+EtOH+VitC group, 10 rats in each group. TBI model was established, and 24 h after TBI, the neurological injury score, brain water content and Evans blue content were measured. Western blot was used to evaluate the expressions of P450 (CYP2E1), AQP-4, MMP-9 and Occludin in the tissue of the damaged brain 24 h after TBI with alcohol consumption.

Results

After 24 h of percussion, the neurological injury score, brain water content and Evans blue content of TBI+EtOH group were significantly increased, after VitC intervention, the indexes were significantly reduced, the difference among the groups was statistically significant (P<0.05); compared with TBI+EtOH group, the expression of CYP2E1, AQP-4 and MMP-9 were decreased, the content of occludin was increased, and the difference between the groups was statistically significant (P<0.05).

Conclusion

Acute ethanol intake aggravates cytotoxic brain edema after TBI, while VitC can reduce the activation of AQP-4 and MMP-9 through CYP2E1, increase the expression of occludin protein, reduce the breakdown of tight connection of blood-brain barrier and the destruction of integrity, reduce the opening of blood-brain barrier and reduce brain edema, and ultimately improve neurological function.

Key words: Alcohol consumption, Traumatic brain injury, Vitamin C, CYP2E1

图1 打击区域示意图及骨蜡封闭骨瓣示意图

表1 颅脑损伤24 h后各组大鼠神经功能损伤评分、脑含水量及伊文氏蓝含量的表达水平比较

组别	只数	神经功能损伤评分（分）	脑含水量（%）	伊文氏蓝含量（μg/g）
TBI-only组	10	10.9±0.4	83.6±0.2	8.2±0.2
TBI+EtOH组	10	13.2±0.5^a	85.6±0.3^a	10.7±0.3^a
TBI+VitC组	10	8.1±0.3^b	82.7±0.2^b	5.9±0.1^b
TBI+EtOH+VitC组	10	9.1±0.4^b	84.3±0.2^bc	6.7±0.2^bc
F值	?	30.973	30.009	99.021
P值	?	<0.001	<0.001	<0.001

表1 颅脑损伤24 h后各组大鼠神经功能损伤评分、脑含水量及伊文氏蓝含量的表达水平比较

组别	只数	神经功能损伤评分（分）	脑含水量（%）	伊文氏蓝含量（μg/g）
TBI-only组	10	10.9±0.4	83.6±0.2	8.2±0.2
TBI+EtOH组	10	13.2±0.5^a	85.6±0.3^a	10.7±0.3^a
TBI+VitC组	10	8.1±0.3^b	82.7±0.2^b	5.9±0.1^b
TBI+EtOH+VitC组	10	9.1±0.4^b	84.3±0.2^bc	6.7±0.2^bc
F值	?	30.973	30.009	99.021
P值	?	<0.001	<0.001	<0.001

图2 颅脑损伤后24 h伊文氏蓝在脑组织中大体病理学示意图

图3 MMP-9、AQP-4、CYP2E1和Occludin在不同分组中的蛋白表达量

[1]	Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research[J]. Lancet Neurol, 2017, 16(12): 987-1048.
[2]	Jiang JY, Gao GY, Feng JF, et al. Traumatic brain injury in china[J]. Lancet Neurol, 2019, 18(3): 286-295.
[3]	Mao X, Xie S, Liu B. Neurotrauma in china[J]. World Neurosurg, 2016, 92: 552-558.
[4]	Wu W, Tian R, Hao S, et al. A pre-injury high ethanol intake in rats promotes brain edema following traumatic brain injury[J]. Br J Neurosurg, 2014, 28(6): 739-745.
[5]	Katada R, Nishitani Y, Honmou O, et al. Prior ethanol injection promotes brain edema after traumatic brain injury[J]. J Neurotrauma, 2009, 26(11): 2015-2025.
[6]	Greiffenstein P, Mathis KW, Stouwe CV, et al. Alcohol binge before trauma/hemorrhage impairs integrity of host defense mechanisms during recovery[J]. Alcohol Clin Exp Res, 2007, 31(4): 704-715.
[7]	Kan EM, Ling EA, Lu J. Microenvironment changes in mild traumatic brain injury[J]. Brain Res Bull, 2012, 87(4-5): 359-372.
[8]	张昊，刘佰运，茆翔.抗坏血酸对创伤性脑损伤的保护作用[J].安徽医科大学学报, 2015, 50(12): 1734-1738.
[9]	张昊，茆翔，刘佰运.抗坏血酸对减轻继发性脑损伤作用机制的研究[J].安徽医药, 2016, 16(1): 26-29.
[10]	Simonian NA, Coyle JT. Oxidative stress in neurodegenerative diseases[J]. Annu Rev Pharmacol Toxicol, 1996, 36(1): 83-106.
[11]	Mao X, Hao S, Zhu Z, et al. Procyanidins protects against oxidative damage and cognitive deficits after traumatic brain injury[J]. Brain Inj, 2015, 29(1): 86-92.
[12]	Mao X, Miao G, Tao X, et al. Saikosaponin a protects tbi rats after controlled cortical impact and the underlying mechanism[J]. Am J Transl Res, 2016, 8(1): 133-141.
[13]	Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease[J]. Pharmacol Rev, 2005, 57(2): 173-185.
[14]	Tsenter J, Beni-Adani L, Assaf Y, et al. Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted mri abnormalities, and motor and cognitive functions[J]. J Neurotrauma, 2008, 25(4): 324-333.
[15]	Yamamoto M, Ramirez SH, Sato S, et al. Phosphorylation of claudin-5 and occludin by rho kinase in brain endothelial cells[J]. Am J Pathol, 2008, 172(2): 521-533.
[16]	Pierce DR, Cook CC, Hinson JA, et al. Are oxidative mechanisms primary in ethanol induced purkinje neuron death of the neonatal rat?[J]. Neurosci Lett, 2006, 400(1-2): 130-134.

[1]	王守森, 傅世龙, 鲜亮, 林珑. 深入理解控制性减压技术对创伤性颅脑损伤术中脑膨出的预防机制与效果[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(05): 257-262.
[2]	吴东阳, 林向丹, 石佐林, 赵玉龙, 王振, 文安国, 纪鑫, 李俊之, 赵明光. NF-L、NLRP3、S100B 蛋白在颅脑损伤严重程度及预后评估中的应用价值[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(05): 279-285.
[3]	罗磊, 熊建平, 郑宏伟, 王嗣嵩, 柴祥, 吴青, 潘海鹏. 静脉留置针穿刺引流治疗颅骨修补术后硬膜外积液一例报道[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(05): 315-317.
[4]	辛强, 朱文豪, 何川, 李文臣, 陈勃, 王海峰. 神经胶质细胞来源的外泌体miRNAs对创伤性颅脑损伤后神经炎症的影响[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(03): 169-173.
[5]	毛进鹏, 陶治鹤, 刘琦, 王勇, 周明安, 陈劲松, 田少斌. 保守治疗大量创伤性硬膜外血肿的体会（附10例报告）[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(03): 164-168.
[6]	从长春, 王春琳, 武孝刚, 王金标, 章福彬, 孙磊, 王李. 重型颅脑损伤患者呼吸机相关性肺炎的危险因素及病原学分析[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(03): 151-157.
[7]	鹿海龙, 朱玉辐, 贺雪凤, 蔡廷江, 王栋, 朱圣玲, 张恩刚, 王策. 创伤性颅脑损伤二次手术的危险因素分析及预警模型构建[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(02): 97-101.
[8]	李鑫, 刘炳辉, 程名, 王凡, 刘玉明, 周绍明. 基于Rotterdam CT评分评估的颅脑损伤术中控制性减压的临床应用价值[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(01): 16-21.
[9]	刘彪, 巍山, 关永胜. 基于Rotterdam CT评分及凝血功能指标的创伤性颅脑损伤预后预测模型的构建与验证[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(01): 22-27.
[10]	罗丹, 柏宋磊, 易峰. HMGB1-TLR2/TLR4/RAGE通路与颅脑损伤并发认知功能障碍病情变化的关系研究[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(01): 28-34.
[11]	袁宝玉, 管义祥, 王东流, 陆正. 不同时机颅骨修补术治疗颅脑外伤的临床疗效[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(01): 35-41.
[12]	唐春雨, 李倩, 郭姗姗, 叶奇, 张丹. 创伤性颅脑损伤神经生理学特征[J/OL]. 中华神经创伤外科电子杂志, 2023, 09(06): 367-371.
[13]	张卓媛, 杨二万, 田志成, 包明冬, 罗鹏. 慢性创伤性脑病的研究新进展[J/OL]. 中华神经创伤外科电子杂志, 2023, 09(06): 360-366.
[14]	聂玉金, 曹培成. 创伤性颅脑损伤患者保守治疗发生脑积水的危险因素分析[J/OL]. 中华神经创伤外科电子杂志, 2023, 09(06): 355-359.
[15]	胡志恒, 任洪波, 宋志远, 张运刚, 韩晓正. 血清sTIM-3及其配体Gal-9、CEACAM-1与创伤性颅脑损伤患者脑损伤程度及预后的关系[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 201-207.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Effect of vitamin C for the pre-injury high ethanol intake in rats following traumatic brain injury

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Effect of vitamin C for the pre-injury high ethanol intake in rats following traumatic brain injury