【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。更多还原

【Abstract】 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 P<0.05). 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 P<0.05).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.更多还原