依达拉奉对大鼠脑创伤后神经细胞凋亡信号通路的影响  

Effect of Edaravone on neurons apoptotic signal pathway in rats after brain trauma

作　　者：赵雅宁[1] 高俊玲[1] 李丽娜[1] 安超旺[1] 田艳霞[1] 崔建忠[2] 

机构地区：[1]华北煤炭医学院基础医学部,唐山063000 [2]唐山市工人医院

出　　处：《临床神经病学杂志》2010年第3期195-198,共4页Journal of Clinical Neurology

基　　金：河北省自然科学基金(c200901247);河北省博士基金(06547008D-7);中国人事部留学归国基金(2007-17)

摘　　要：目的探讨依达拉奉对脑创伤后神经细胞凋亡信号通路的影响。方法 135只雄性SD大鼠随机分为对照组(25只)、创伤组(60只)和依达拉奉组(50只)。Marmarous法建立SD大鼠弥漫性脑创伤模型;依达拉奉组大鼠伤后即刻经尾静脉注射依达拉奉10mg/kg,每天1次,共3d;分别于伤后1h、6h、24h、48h和72h采用硫代巴比妥酸法检测大脑皮质中丙二醛(MDA)含量;免疫组化法和WesternBlot法检测皮质区磷酸化细胞外信号调节激酶(ERK1/2)及细胞色素C(CytC)的表达;原位缺口末端标记法(TUNEL)检测神经细胞凋亡。伤后24h、48h、72h对大鼠综合运动功能进行评定。结果与对照组比较,创伤组大鼠脑组织MDA水平(6h、24h、48h、72h)、磷酸化ERK1/2(1h、6h、24h、48h)和CytC(6h、24h、48h、72h)表达明显增高,细胞凋亡数(6h、24h、48h、72h)增多;综合运动能力评分下降(均P<0.05)。与创伤组比较,依达拉奉组大鼠脑组织MDA含量、磷酸化ERK1/2和CytC表达、神经细胞凋亡数下降;大鼠的运动功能评分回升(均P<0.05)。结论依达拉奉通过清除氧自由基、抑制ERK1/2信号途径活化、减少神经细胞凋亡而发挥对脑创伤的保护作用。Objective To investigate the effect of Edaravone on neuron apoptosis signal pathway in rats after brain trauma. Methods 135 male SD rats were divided randomly into control group （n=25）,trauma group （n=60）,Edaravone group （n=50）. Rat model after brain trauma was established by Marmarou＇s diffused brain injury method. Instantly after the brain injury,the rats in Edaravone group were injected Edaravone 10 mg/kg by caudal vein,and once a day,for 3 d. At 1 h,6 h,24 h,48 h and 72 h after injury,the malondialdehyde （MDA） contents in brain were measured by spectrophotometry; the ERK1/2 phosphorylation and CytC expression were detected by immunohistochemistry and Western Blot; the quantity of neuron apoptosis was observed with TUNEL method. Behavioral test were performed at 24 h,48 h,72 h post trauma.Results Compared with control group,the MDA contents（6 h,24 h,48 h and 72 h post trauma）,the expression of ERK1/2 phosphorylation（1 h,6 h,24 h,48 h）,CytC（6 h,24 h,48 h,72 h）and the number of apoptotic nerve cells（6 h,24 h,48 h,72 h）were significantly increased in trauma group; the scores of behavioral test were significantly decreased （all P0.05）. Compared with trauma group,the MDA contents,the expression of ERK1/2 phosphorylation,CytC and the number of apoptotic neuron were obviously decreased in Edaravone group; meanwhile,the scores of behavioral test were increased （all P0.05）.Conclusion Edaravone can scavenge oxygen free radical,down-regulate ERK1/2 signal pathway activation and reduce neuron apoptosis,thus to improve function after brain trauma.

关 键 词：脑创伤 依达拉奉 细胞外信号调节激酶MAP类 细胞色素C 凋亡 

分 类 号：R651.1[医药卫生—外科学]