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目的探讨依达拉奉(Edaravone)对弥漫性脑创伤后认知功能障碍的治疗作用及其机制。方法随机将SD大鼠分为对照组(40只)、创伤组(68只)、Edaravone干预组(68只)。Marmarou′s法建立SD大鼠弥漫性脑创伤模型。在电镜下观察伤后1、6、24、48、72 h线粒体形态结构变化;采用免疫组化和Western blot法检测上述时间点磷酸化细胞外信号调节激酶1/2(p-ERK1/2)和Cytc的表达;伤后第3天水迷宫法测试动物学习记忆功能,连测7 d。结果伤后海马区部分神经细胞线粒体肿胀、内脊断裂、消失;免疫组化显示p-ERK1/2和细胞色素C(Cytc)阳性产物主要定位于细胞浆,Western blot定量显示,伤后p-ERK1/2和Cytc表达水平增高,分别于24、48 h达高峰;水迷宫实验显示,创伤组大鼠搜索安全岛潜伏期(230.9±20.9)s明显高于对照组(50.7±4.9)s;Edaravone治疗组线粒体受损程度、p-ERK1/2和Cytc表达水平以及搜索安全岛潜伏期(70.6±8.7)s均低于创伤组。结论Edaravone对弥漫性脑创伤有治疗作用,其机制与抑制伤后ERK12活化、减轻线粒体形态结构损伤、减少Cytc释放有关。
Objective To investigate the therapeutic effect of edaravone on cognitive dysfunction after diffuse brain injury and its mechanism. Methods SD rats were randomly divided into control group (n = 40), trauma group (n = 68) and Edaravone intervention group (n = 68). Establishment of diffuse brain injury model in SD rats by Marmarou ’s method. The morphological changes of mitochondria at 1, 6, 24, 48 and 72 h after injury were observed under electron microscope. The expressions of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1 / 2) And Cytc expression; on the third day after injury, the water maze method was used to test the learning and memory function of animals, even for 7 days. Results The mitochondria of some neurons in the hippocampus were swollen and the internal crests ruptured and disappeared. Immunohistochemistry showed that the positive products of p-ERK1 / 2 and Cytc were located in the cytoplasm. Western blot showed that p- ERK1 / 2 and Cytc expression reached the peak at 24 and 48 h, respectively. The water maze test showed that the search latency (230.9 ± 20.9) s in the traumatic group was significantly higher than that in the control group (50.7 ± 4.9) s; Edaravone treatment Mitochondria damage, p-ERK1 / 2 and Cytc expression levels, and search for the island latency (70.6 ± 8.7) s were lower than those in the trauma group. Conclusion Edaravone has a therapeutic effect on diffuse brain injury. Its mechanism is related to inhibiting the activation of ERK12, mitigating the mitochondrial morphological damage and reducing the release of Cytc.