虎纹捕鸟蛛毒素-I对全脑缺血再灌损伤大鼠海马组织中TNF凋亡通路的影响

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目的:探讨注射虎纹捕鸟蛛毒素-I(HWTX-I)对全脑缺血模型大鼠神经保护作用的可能分子机制。方法:48只SD大鼠随机分为假手术组、非用药组和用药组,采用改良的Pulsinelli大鼠四血管阻断全脑缺血结合蛛网膜下腔置管模型,应用光镜、免疫组化方法观察各组大鼠海马CA1区锥体细胞Nissl染色形态学变化及海马组织中肿瘤坏死因子α(TNFα)、肿瘤坏死因子受体I(TNFRI)、TNF相关死亡结构域(TRADD)、Fas相关死亡结构域(FADD)、Caspase8等TNF凋亡通路相关因子蛋白表达水平的变化。结果:(1)用药组大鼠锥体神经元排列较整齐,略为疏散分布,而非用药组大鼠锥体神经元排列散乱,层次不完整,稀疏分布;(2)TNFα、TNFRI、TRADD、FADD、Caspase8阳性单位的表达值以非用药组最高,用药组次之,假手术组表达最低。结论:HWTX-I能明显减轻全脑缺血再灌损伤大鼠海马锥体细胞的损伤,并降低大鼠海马组织TNFα、TNFRI、TRADD、FADD、Caspase8蛋白水平表达,表明HWTX-I对全脑缺血再灌损伤大鼠海马神经细胞凋亡具有抑制作用,在一定程度上对全脑缺血再灌损伤有神经细胞保护作用。 Objective: To investigate the possible molecular mechanism of HWTX-I on neuroprotection in rats with global cerebral ischemia. Methods: Forty-eight Sprague-Dawley rats were randomly divided into sham-operation group, non-treatment group and treatment group. The rats were implanted with modified Pulsinelli’s four-vessel occlusion model of global cerebral ischemia and subarachnoid space. Methods Nissl staining of hippocampal CA1 pyramidal cells in hippocampus was observed in each group. The changes of TNF-α, TNFR, TRADD, Related death domain (FADD), Caspase8 TNF apoptosis pathway related protein expression levels. Results: (1) The pyramidal neurons in the treatment group were arranged in a neat and slightly scattered manner, while the neurons in the non-treatment group were disordered and distributed in an uneven and sparsely distributed manner. (2) The expressions of TNFα, TNFRI, TRADD, The expression of FADD and Caspase8 positive units was the highest in the non-medication group, followed by the medication group, and the lowest in the sham-operated group. Conclusion: HWTX-I can significantly reduce the damage of hippocampal pyramidal cells and decrease the expression of TNFα, TNFRI, TRADD, FADD and Caspase8 in rat hippocampus after global cerebral ischemia-reperfusion injury, indicating that HWTX- Ischemia-reperfusion injury in rat hippocampal neuronal apoptosis has an inhibitory effect, to a certain extent, has a protective effect of nerve cells on global cerebral ischemia-reperfusion injury.
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