依达拉奉对大鼠弥漫性脑创伤后认知功能及ERK1/2活化、Cytc释放的影响

山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (11): 34-37.

依达拉奉对大鼠弥漫性脑创伤后认知功能及ERK1/2活化、Cytc释放的影响

赵雅宁^1，2，张文丽¹，高俊玲¹，饶颖臻³，田艳霞¹，尹立国⁴，崔建忠⁴

1. 华北煤炭医学院基础医学部组织学与胚胎学教研室河北省煤矿卫生与安全实验室；
2. 华北煤炭医学院护理系； 3. 华北煤炭医学院附属医院神经外科；
4. 唐山市工人医院神经外科，河北唐山 063000

收稿日期:2009-03-15 发布日期:2009-11-16
通讯作者: 高俊玲（1962- ），硕导，主要从事脑损伤与脑保护的研究。Email：junlinggao@163.com
作者简介:赵雅宁（1974- ），硕士，主要从事脑损伤与脑保护的研究。 Email：zynning789@126.com
基金资助:
河北省博士基金资助项目(06547008D7)；中国人事部留学归国基金资助项目(200717)。

Effect of Edaravone on cognition ERK1/2 activation and Cytc
release after traumatic brain injury in rats

ZHAO Yaning ^1，2，　ZHANG Wenli ¹，　GAO Junling ¹，　Rao Yingzhen ³，　
TIAN Yanxia ¹，　YIN Liguo ⁴, CUI Jianzhong ⁴

1. Department of Histology & Embryology, Hebei Key Laboratory of Occupational Health and Safety for Coal Industry;
2. Department of Nursing, Affiliated Hospital of North China Coal Medical College;
3. Department of Neurosurgery, Affiliated Hospital of North China Coal Medical College；
4. Department of Neurosurgery, Tangshan Gongren Hospital， Tangshan 063000， Hebei， China

Received:2009-03-15 Published:2009-11-16

摘要/Abstract

摘要：

目的探讨依达拉奉(Edaravone)对弥漫性脑创伤后认知功能障碍的治疗作用及其机制。方法随机将SD大鼠分为对照组(40只)、创伤组(68只)、Edaravone干预组(68只)。Marmarou′s法建立SD大鼠弥漫性脑创伤模型。在电镜下观察伤后1、6、24、48、72?h线粒体形态结构变化；采用免疫组化和Western blot法检测上述时间点磷酸化细胞外信号调节激酶1/2（pERK1/2）和Cytc的表达；伤后第3天水迷宫法测试动物学习记忆功能，连测7?d。结果伤后海马区部分神经细胞线粒体肿胀、内脊断裂、消失；免疫组化显示 pERK1/2和细胞色素C（Cytc）阳性产物主要定位于细胞浆，Western blot定量显示，伤后pERK1/2和Cytc表达水平增高，分别于24、48?h达高峰；水迷宫实验显示，创伤组大鼠搜索安全岛潜伏期（230.9±20.9）s明显高于对照组（50.7±4.9）s；Edaravone治疗组线粒体受损程度、pERK1/2和Cytc表达水平以及搜索安全岛潜伏期（70.6±8.7）s均低于创伤组。结论Edaravone对弥漫性脑创伤有治疗作用，其机制与抑制伤后ERK12活化、减轻线粒体形态结构损伤、减少Cytc释放有关。

关键词: 脑损伤；有丝分裂素激活蛋白激酶类；细胞色素C；依达拉奉

Abstract:

Abstract： ObjectiveTo study the effects of Edaravone on cognitive function and its potential mechanism after traumatic brain injury. MethodsMale SpragueDawley rats were randomly divided into the control group（n=40），　the traumatic group（n=68），　and the Edaravone treatment group（68）. TBI rat models were established based on description of the Marmarou′s diffused brain injuries. At 1，6，24，48，72?h after injuries， the histopathological changes of mitochondria were observed with an electron microscope. Expressions of pERK1/2 and Cytc were determined by immunohistochemistry and WesternBlot. Learning and memory functions (Morris water maze) were determined daily 3?d after injuries for 7?d. ResultsAfter TBI， some mitochondria displayed swelling, spinal fracture, or even disappeared. Expression of pERK1/2 increased with the development of TBI and peaked at 24 h, then gradually decreased and expression of Cytc increased and peaked at 48?h. The searching safety island period山of rats in the traumatic group(230.9±20.9) was significantly longer than that of rats in the control group(50.7±4.9). While the histopathological damages of mitochondria and expressions of pERK1/2 and Cytc were significant decreased in the Edaravone treatment group, and the searching safety island period (130.0±30.8) was markedly restored(P＜0.05). ConclusionEdaravone has good therapeutic effect on traumatic brain injury and the molecular mechanism is related to attenuating ERK1/2 activation and Cytc release following the trauma.

Key words: Brain injuries； Mitogenactivated protein kinases； Cytochrome c； Edaravone

中图分类号:

R651

赵雅宁1，2，张文丽1，高俊玲1，饶颖臻3，田艳霞1，尹立国4，崔建忠4. 依达拉奉对大鼠弥漫性脑创伤后认知功能及ERK1/2活化、Cytc释放的影响[J]. 山东大学学报(医学版), 2009, 47(11): 34-37.

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