大鼠弥漫性轴索损伤后氧化应激对谷氨酸兴奋性毒性的影响及其机制

目的探讨大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后脑内氧化应激对谷氨酸兴奋性毒性的影响及其作用机制。方法采用大鼠头部瞬间旋转损伤装置制备DAI模型,通过促氧化剂SIN-1及抗氧化剂GSH干预控制DAI大鼠脑内氧化应激水平,对大鼠进行神经功能缺损评分(modified neurological severity scores,mNSS),检测脑干组织内超氧化物歧化酶(superoxide dismutase,SOD)活力、丙二醛(malondialdehyde,MDA)含量和谷氨酸(glutamate,Glu)含量,Western blot法测定谷氨酸转运体-1(...

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Published in西安交通大学学报(医学版) Vol. 36; no. 1; pp. 60 - 64
Main Author 白立曦 宋锦宁 黄延钦 李丹东 翟海程 罗显华 赵永林
Format Journal Article
LanguageChinese
Published 西安交通大学医学院第一附属医院神经外科,陕西西安,710061 2015
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ISSN1671-8259
DOI10.7652/jdyxb201501010

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Summary:目的探讨大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后脑内氧化应激对谷氨酸兴奋性毒性的影响及其作用机制。方法采用大鼠头部瞬间旋转损伤装置制备DAI模型,通过促氧化剂SIN-1及抗氧化剂GSH干预控制DAI大鼠脑内氧化应激水平,对大鼠进行神经功能缺损评分(modified neurological severity scores,mNSS),检测脑干组织内超氧化物歧化酶(superoxide dismutase,SOD)活力、丙二醛(malondialdehyde,MDA)含量和谷氨酸(glutamate,Glu)含量,Western blot法测定谷氨酸转运体-1(glutamate transporter-1,GLT-1)的表达水平。结果损伤组在6、24、72h的mNSS评分值均高于假损伤组(P〈0.05)。与假损伤组相比,损伤组大鼠在各时间点脑干SOD活力均降低,MDA含量均升高(P〈0.05);与DAI+NS组相比,DAI+SIN-1组24h及72hSOD活力均降低、MDA含量均升高(P〈0.05),而DAI+GSH组变化相反(P〈0.05)。与假损伤组相比,损伤组在各时间点脑干细胞内Glu含量均有所降低(P〈0.05);与DAI+NS组相比,DAI+SIN-1组在各时间点细胞内Glu含量明显降低(P〈0.05),DAI+GSH组在24h细胞内Glu含量有所升高(P〈0.05)。DAI后24h及72h损伤组GLT-1表达水平较假损伤组均降低(P〈0.05),同时DAI+SIN-1组GLT-1表达水平均低于DAI+NS组(P〈0.05),而DAI+GSH组在72h时GLT-1表达高于DAI+NS组(P〈0.05)。结论大鼠DAI后脑内氧化应激可降低神经细胞膜GLT-1的表达水平,抑制Glu的回摄取,从而加重细胞外Glu堆积,增强谷氨酸兴奋性毒性作用。
Bibliography:BAI I.i-xi, SONG Jin ning, HUANG Ting-qin, LI Dan dong, ZHAI Hai-eheng, I.UO Xian hua, ZHAO Yong-lin (Department of Neurosurgery, the First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710061, China)
diffuse axonal injury; oxidative stress; glutamate excitotoxicity; rat; traumatic brain injury
Objective To explore the potential effect and its mechanism of oxidative stress on glutamate excitotoxicity after diffusc axonal injury (DAI) in rats. Methods An instantaneous rotation head damage device was used to build the rat DAI model. 3-morpholino-sydnonimine (SIN-l) and glutathione (GSH) were respectively administered as pro-oxidant and anti-oxidant to induce different levels of oxidative stress. Rats were scored by the modified neurological severity scores (mNSS); the concentration of superoxide dismutase (SOD), malondialdehyde (MDA) and glutamate (Glu) in rats' brain stem were respectively determined, and the expression level of GLT-1 was detected by Western blot. Results The mNSS score
ISSN:1671-8259
DOI:10.7652/jdyxb201501010