依达拉奉对大鼠重型弥漫性脑创伤后细胞外信号调节激酶1/2信号通路的影响  被引量:6

Effect of edaravone on extracellular signal-regulated kinase 1/2 pathway following severe traumatic brain injury in rats

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作  者:赵雅宁[1] 郭霞[1] 高俊玲[1] 陈海红[1] 田艳霞[1] 崔建忠[2] 

机构地区:[1]华北煤炭医学院,河北唐山063000 [2]唐山市工人医院

出  处:《中国危重病急救医学》2010年第4期230-233,共4页Chinese Critical Care Medicine

基  金:河北省自然科学基金(2009001247);人事部留学归国基金(2007-17);河北省博士基金(06547008D-7)

摘  要:目的探讨依达拉奉对重型弥漫性脑创伤(TBI)的保护作用及其机制。方法273只雄性SD大鼠按随机数字表法分为对照组(45只)、模型组(88只)及依达拉奉低剂量组(72只)、高剂量组(68只)。采用重物撞击致大鼠TBI模型。伤后1、6、24、48和72h,在光镜和电镜下观察脑组织病理变化;用蛋白质免疫印迹法(Western blotting)检测磷酸化细胞外信号调节激酶1/2(ERK1/2)表达;用免疫组化法和原位末端缺刻标记法(TUNEL)检测神经细胞凋亡情况。伤后7~10d应用水迷宫对大鼠学习记忆能力进行评定。结果与对照组比较,伤后6、24、48、72h海马区部分神经细胞出现变性、坏死,1、6、24、48h磷酸化ERK1/2表达水平(pg/U)显著增高(分别为:2.05±0.40、4.40±0.96、6.70±0.87、3.67±0.28比0.40±0.04、0.41±0.05、0.43±0.06、0.40±0.03),6、24、48、72h神经细胞凋亡数(个)明显增多(分别为:9.60±2.69、12.68±2.99、16.94±3.92、25.82±4.61比2.42±0.38、2.58±0.57、2.74±0.56、2.61±0.58),7~10d大鼠搜索安全岛潜伏期(s)延长(分别为:119.8±25.0、105.6±24.5、98.5±21.8、92.0±19.5比49.5±7.5、32.7±6.3、25.8±6.5、24.8±5.5,均P〈0.05)。应用依达拉奉干预后,脑组织损伤程度、磷酸化ERK1/2表达水平降低,神经细胞凋亡数回降,大鼠搜索安全岛潜伏期缩短(依达拉奉低剂量组磷酸化ERK1/2表达6、24、48h分别为:2.46±0.22、4.00±0.84、2.38±0.32,高剂量组分别为:1.67±0.15、1.86±0.38、1.27±0.28;依达拉奉低剂量组凋亡细胞数6、24、48、72h分别为:5.20土1.23、7.10±1.72、9.54±1.36、14.12±3.19,高剂量组分别为:3.40±0.49、4.39±0.73、5.02±1.12、8.78±2.16;依达拉奉低剂量组潜伏期7~10d分别�Objective To study the protective effect of edaravone on severe traumatic brain injury (TBI) and its potential mechanism. Methods Two hundred and seventy-three male Sprague-Dawley (SD) rats were divided randomly into four groups: control group (n = 45), model group (n = 88), low-dose edaravone treatment group (n = 72), high-dose edaravone treatment group (n= 68). TBI rat model was reproduced by weight-dropping injury. One, 6, 24, 48 and 72 hours after injury, changes in brain tissue were observed with light and electron microscopy. The expression of phosphorylated extraeellular signal-regulated kinase 1/2 (p-ERK1/2) was determined by Western blotting. The rate of neuron apoptosis was observed with immunohistochemistry and terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Learning and memory function assessments were performed with Morris water maze from 7th day to 10th day after injury. Results Compared with control group, a part of neurons in hippocampus displayed histopathologic changes denoting necrosis 6, 24, 48 and 72 hours after injury. The p-ERK1/2 expression level (pg/unit)increased 1, 6, 24, 48 hours after injury (2. 05±0.40, 4.40±0. 96, 6.70±0.87, 3.67±0.28 vs. 0.40±0.04, 0.41±0.05, 0.43±0.06, 0.40±0.03), and the number of apoptotic cells increased 6, 24, 48, 72 hours after injury (9.60±2.69, 12. 68±2.99, 16. 94±3.92, 25. 82±4. 61 vs. 2.42±0. 38, 2. 58±0.57, 2.74±0.56, 2. 61±0.58); latent period to find the safety platform (s) was significantly prolonged (119. 8±25.0, 105.6±24. 5, 98.5±21.8, 92. 0±19.5 vs. 49. 5±7. 5, 32. 7± 6.3, 25.8±6.5, 24.8±5.5, all P〈0.05). After treatment with edaravone, the degree of morphological injury, p-ERK1/2 level and number of apoptotic neurons decreased, latent period to find the safety platform was significantly shortened (in low-dose edaravone treatment group, p-ERK1/2 expression level at 6, 24, 48 hours was 2.46±0. 22, 4. 00±0.84, 2. 38±0. 32, and

关 键 词:脑创伤 弥漫性 细胞外信号调节激酶 凋亡 学习 记忆 

分 类 号:R651.1[医药卫生—外科学]

 

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