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

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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]. 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]. 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

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