Edaravone对大鼠脑创伤后ERK1/2信号通路及神经细胞凋亡的影响  

Effect of Edaravone on ERK1/2 signal pathway and cell apoptosis following traumatic brain injury in rats

作　　者：赵雅宁[1,2] 邓银侠[1] 崔建忠[3] 张宇新[1] 高俊玲[1] 

机构地区：[1]华北煤炭医学院基础部河北省煤矿卫生与安全重点实验室,河北唐山063000 [2]华北煤炭医学院护理学系,河北唐山063000 [3]唐山市工人医院,河北唐山063000

出　　处：《基础医学与临床》2009年第9期933-937,共5页Basic and Clinical Medicine

基　　金：河北省博士基金(06547008D-7);中国人事部留学归国基金(2007-17)

摘　　要：目的探讨Edaravone对脑创伤后ERK1/2信号通路及神经细胞凋亡的影响及其机制。方法用Marmarou s法建立SD大鼠中度弥漫性轴索损伤模型（n=120）,随机分为3组：（1）假手术对照组（A组,n=24）、（2）创伤组（B组,n=48）、（3）Edaravone干预组（C组,n=48）。分别在伤后1、6、24、48和72 h 5个时相点收取脑组织标本,硫代巴比妥酸法检测大脑皮质中MDA含量;Western-blot法检测皮质区p-ERK1/2活性;免疫组化法检测p-ERK1/2、BAX和BCL-2蛋白的表达;TUNEL法标记神经细胞凋亡数。计算机图像分析系统进行定量分析。结果与假手术组比较,创伤组中MDA含量（伤后6～72 h）、ERK1/2（p-ERK1/2）活性（伤后1～48 h）、BAX/BCL-2比值（伤后6～48 h）及凋亡的神经细胞数目（伤后6～72 h）显著增高（P〈0.05）;Edaravone干预显著缓解上述改变（P〈0.05）。结论Edaravone可减少脑创伤后的神经细胞凋亡,其机制与其可清除氧自由基、抑制ERK1/2通路活化有关。Objective To study the effect and potential mechanism of Edaravone on extracellular signal-regulated kinase 1/2 （ERK1/2） signal pathway and neuron apoptosis after traumatic brain injury（TBI）. Methods Male Sprague-Dawley rats（ n = 120） were randomly divided into three groups： sham operation group （A group ,n = 24 ）, traumatic group （B group, n =48）, Edaravone treatment group （C group, n = 48 ）. TBI rat model was established according to the description of Marmarou＇s diffused brain injury. At different time points（ 1,6,24,48 and 72 h） after operation, the malondialdehyde （MDA） in cortex were measured with spectrophotometry, p-ERK1/2, BAX and BCL-2 were detected by immunohistochemistry and Western blot, neuron apoptosis were quantitatively examined with TUNEL method. Results Compared with sham group, MDA contents （6 -72 h post trauma）, the expression levels of p-ERK1/2（ 1 -48 h post trauma） ,the rates of BAX/BCL-2（6 -48 h post trauma） and the apoptotic cells （6 ～ 72 h post trauma） in the cortex were significantly increased （P 〈 0.05 ） following TBI ; Compared with traumatic group, the above mentioned indexes in Edaravone treatment group were decreased significantly（ P 〈 0. 05 ）. Conlusion Edaravone can dramatically alleviate neuron apoptosis. The one of mechanisms is related to its scavenging oxygen free radical and down-regulation of ERK1/2 signal pathway.

关 键 词：脑创伤 依达拉奉 细胞外信号调节激酶1/2 细胞凋亡 

分 类 号：R96[医药卫生—药理学]