依达拉奉对大鼠弥漫性脑创伤后ERK1/2通路及神经细胞凋亡的影响  

Effects of Edaravone on ERK1/2 signal pathway and neurocyte apoptosis after diffuse brain injury in rats

作　　者：赵雅宁[1] 高俊玲[1] 李丽娜[1] 陈海红[1] 刘兴宇[2] 崔建忠[2] 

机构地区：[1]华北煤炭医学院基础医学部 河北省煤矿卫生与安全实验室,河北唐山063000 [2]唐山市工人医院神经外科

出　　处：《解放军医学杂志》2009年第9期1093-1097,共5页Medical Journal of Chinese People's Liberation Army

基　　金：河北省自然科学基金(C2009001247);河北省科技领军人才基金(06547008D-7);中国人力资源和社会保障部留学人员科技活动项目择优资助基金(2007-17)

摘　　要：目的探讨脑创伤后细胞外信号调节激酶1/2(ERK1/2)信号调控神经细胞凋亡的分子机制及依达拉奉(Edaravone)的治疗作用。方法SD大鼠随机分为对照组、脑创伤组、U0126干预组、Edaravone治疗组。Marmarou法建立大鼠弥漫性脑创伤模型。U0126干预组于大鼠伤前30min经尾静脉注射U0126(0.1mg/kg),每24h注射1次,连续3d;Edaravone治疗组分高、中、低剂量组,于伤后10min经尾静脉注射Edaravone(3、6、10mg/kg),每24h注射1次,连续3d。对照组不致伤。光镜和电镜下观察伤后脑组织形态变化;Western blotting法检测伤后1、6、24、48、72h磷酸化ERK1/2和Bax的表达,原位缺口末端标记法(TUNEL)检测上述时间点神经细胞的凋亡。伤后24、48、72h对大鼠的综合运动功能进行评定。结果致伤后,大鼠皮质区部分神经细胞出现变性坏死和凋亡改变;神经细胞凋亡数目和Bax表达显著增多,伴随磷酸化ERK1/2水平增加,神经运动功能评分下降。应用U0126和Edaravone干预后,神经细胞形态损伤程度减轻;神经细胞凋亡数目和Bax表达回降,磷酸化ERK1/2水平降低;神经运动功能评分升高,上述改变在U0126和高、中剂量Edaravone组中差异显著(P<0.05)。结论脑创伤后活化ERK1/2信号通过调控Bax在神经细胞凋亡过程中发挥重要作用;Edaravone通过抑制ERK1/2信号途径,减少神经细胞凋亡发挥保护作用。Objective To study the molecular mechanism of neurocyte apoptosis induced by activated extraceUular signal-regulated kinase 1/2 （ERK1/2） after diffuse brain injury （DBI）, and the possible protective mechanism of Edaravone on brain trauma in rats. Methoth Two htmdred and sixty-four male Sprague-Dawley rats were assigned into control group （n=24）, model group （n=48）, U0126 treatment group （n= 48） and 3 Edaravone treatment groups （48 each）. DBI rat model was reproduced with Marmarous method. In U0126 treatment group, rats were intravenously injected with U0126 （0. 1mg/kg） 30 min before injury, and every 24 h for 3d. In the 3 Edaravone treatment groups, rats were injected with Edaravone in different doses （3mg/kg, 6mg/kg and 10mg/kg, respectively） 10min post-injury and every 24h for 3d. Rats in control group were not injured. At different time points after injury, the histopathological changes in neurocytes were observed with light and electron microscopy. The expressions of phosphorylated ERK1/2 and Bax were measured by Western blotting. Apoptosis was determined with TUNEL method. Behavioral tests were performed at 24, 48 and 72h time points. Results After DBI, rats displayed necrosis of neurocytes, increased expressions of Bax and apoptosis, accompanied by an elevated level of phosphorylated ERK1/2. The scores of motor function were decreased. After treatment with U0126 and Edaravone, the histopathological damage of neurocytes was ameliorated, the expressions of Bax and the number of apoptotic cells were significantly decreased in U0126 group as well as in rniddie and high dosage of Edaravone groups compared with the traumatic group, accompanied by the decreased level of phosphorylated ERK1/2. Meanwhile, the neuroscores of behavior were enhanced. Conclusions Edaravone can dramatically improve the brain function and reduce neurocyte apoptosis after DBI. One of the molecular mechanisms may be related to the down-regulation of ERK1/ 2 signal pathway.

关 键 词：依达拉奉 头部损伤 穿透性 细胞外信号调节MAP激酶类 细胞凋亡 

分 类 号：R651[医药卫生—外科学]