干预癫痫大鼠自噬活性对小胶质细胞激活状态及肿瘤坏死因子-α分泌的影响及意义

发布时间：2019-01-05 22:02

【摘要】：目的观察干预癫痫大鼠自噬活性对小胶质细胞激活状态及分泌肿瘤坏死因子-α(TNF-α)水平变化的影响,探讨其对神经元以及癫痫状态的影响。方法 Wistar大鼠随机分为正常对照组(6只)与癫痫组(24只);癫痫组大鼠采用戊四氮制作癫痫模型,造模成功后随机分为致痫对照组、3-甲基嘌呤(3-MA)组及雷帕霉素(RAPA)组,每组各6只。观察记录各组大鼠行为学及脑电图变化,采用HE及Nissl染色观察CA1区神经元损伤情况,免疫荧光染色及Western blot检测海马组织LC3、CD68及TNF-α的表达。结果致痫对照组显示癫痫可导致神经元损伤,LC3、CD68、TNF-α的表达较正常对照组显著增加(P0.05)。3-MA组与致痫对照组相比癫痫发作等级降低;神经元损伤数目减少;LC3、CD68、TNF-α的表达显著降低(P0.05)。RAPA组大鼠癫痫发作等级、CD68和TNF-α的表达较致痫对照组无明显变化(P0.05);但神经元损伤数目及LC3的表达进一步增加(P0.05)。结论癫痫过程中存在自噬现象,其可激活小胶质细胞,促进TNF-α分泌,导致神经元损伤;而抑制自噬活性可调控小胶质细胞,减少TNF-α的分泌,保护神经元,从而减轻癫痫发作状态。
[Abstract]:Objective to observe the effects of autophagy on the activation of microglia and the secretion of tumor necrosis factor- 伪 (TNF- 伪) in epileptic rats. Methods Wistar rats were randomly divided into normal control group (n = 6) and epilepsy group (n = 24). The epileptic rats in the epileptic group were randomly divided into three groups: epileptogenic control group, 3-methylpurine (3-MA) group and rapamycin (RAPA) group, with 6 rats in each group. The changes of ethology and electroencephalogram (EEG) in each group were observed. The neuronal damage in CA1 area was observed by HE and Nissl staining. The expression of LC3,CD68 and TNF- 伪 in hippocampus was detected by immunofluorescence staining and Western blot. Results Epilepsy control group showed that epilepsy could cause neuronal injury, and the expression of LC3,CD68,TNF- 伪 was significantly higher than that of normal control group (P0.05). The grade of epileptic seizure and the number of neuron damage in 3-MA group were lower than those in epileptic control group. The expression of LC3,CD68,TNF- 伪 was significantly decreased (P0.05) in the). RAPA group, but the expression of CD68 and TNF- 伪 was not significantly changed compared with the epileptic control group (P0.05). However, the number of neuronal injury and the expression of LC3 were further increased (P0.05). Conclusion there is autophagy in the course of epilepsy, which can activate microglia, promote the secretion of TNF- 伪, and lead to neuronal injury. Inhibition of autophagy can regulate microglia, reduce the secretion of TNF- 伪, protect neurons and relieve epileptic seizures.
【作者单位】：滨州医学院附属医院;滨州医学院;
【分类号】：R742.1

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