厄多司坦对癫痫大鼠海马氧化应激及肿瘤坏死因子-α、基质金属蛋白酶-2水平的影响

目的]观察厄多司坦对癫痫大鼠海马神经元的病理损伤，分析并对超氧化物歧化酶（SOD）、丙二醛（MDA）、基质金属蛋白酶-2（MMP-2）、肿瘤坏死因子-α（TNF—α）水平的影响．方法]将健康成年雄性Wistar大鼠随机分为正常对照组、模型对照组及厄多司坦干预组．通过反复腹腔注射给予戊四氮建立大鼠癫痫模型，测定各组大鼠海马组织SOD及MDA水平，采用HE染色法观察大鼠癫痫发作后海马神经元的形态学改变，采用ELISA法测定细胞因子TNF—α的含量改变，采用免疫组织化学方法观察MMP-2在海马组织中的分布．结果]HE染色结果显示，模型对照组海马区神经元细胞出现核固缩、碎裂和溶解，细胞坏死、脱失明显；厄多司坦干预组以神经元变性为主，神经细胞坏死数量较模型对照组明显减少（P〈0．01）．模型对照组大鼠海马SOD活性较正常对照组及厄多司坦干预组均明显降低（P〈0．01）；模型对照组MDA，TNF-α及MMP．2水平均较正常对照组明显升高（P〈0．01），厄多司坦干预组均较模型对照组水平明显降低（P〈0．01）．结论]癫痫发作时伴有氧化应激反应，免疫-神经-内分泌系统及免疫机制参与其中；厄多司坦具有清除氧自由基，减少细胞因子的产生，抑制MMP-2活化，保护癫痫大鼠海马神经元的作用．

Effects of erdosteine on oxidative stress,TNF-a and MMP-2 of hippocampus in epilepsy model of rats

OBJECTIVE To observe the effects of erdosteine on pathologic injury of hippocampal neurons and SOD, MDA, TNF-α and MMP-2 in epilepsy model of rats. METHODS The adult male Wistar rats were randomly divided into normal control, model and erdosteine predisposal treatment groups. Epilepsy model of rats was established by repeatedly intraperitoneal injection with pentetrazole. The activity of SOD and content of MDA in hippocampal tissue were detected by chemical colorimetry, and the pathological changes of hippocampal neurons after epileptic attack were observed by HE staining, and the content of TNF-α were assayed by ELISA, and the distribution of MMP-2 positive cells was observed by immunohistochemistry. RESULTS The karyopyknosis, karyorrhexis, karyolyisis of hippocampal neurons and obvious demyelination were observed in model group, and primarily neurodegeneration was in erdosteine groups, and the number of nerve cells necrosis activity of hippocampal was significantly reduced as compared with normal control group （P〈0.01）. The SOD was lower in model group than in erdosteine and normal control groups （P〈0.01）, and the content of MDA, TNF-α and MMP-2 were significantly higher in model group than in normal control group, and significant lower in erdosteine group than in control group （P 〈 0.01）, and the content of TNF-α were significantly higher in model group than in normal control group, and it was significant lower in erdosteine group than in model group （ P 〈0. 01 ）. CONCLUSION The erdosteine can clear off oxygent free radical, reduces the production of the cytokines, inhibits the activation of MMP-2, and protects the role of hippocampal neurons in epilepsy model of rats.