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目的:研究丙戊酸钠(VPA)对癫痫模型大鼠海马内细胞自噬、动物脑电图和行为学的影响。方法:制作癫痫大鼠模型并随机分为癫痫组、3甲基腺嘌呤(3MA)组、VPA组及VPA联合3MA组四组,设正常大鼠为对照组。观察各组行为学及脑电图变化,HE及Nissl染色显示神经元的损伤情况,免疫组织化学染色、Western Blot、Real-time PCR检测自噬标记物微管相关蛋白1轻链3(LC3)表达。结果:行为学观察及脑电图检测显示,丙戊酸钠组及丙戊酸钠联合3MA组均可降低癫痫发作等级,3MA组无抗癫痫效果。HE及Nissl染色显示,对照组未见明显异常,癫痫组神经元损伤严重,丙戊酸钠组与癫痫组相比,神经元损伤明显减轻;3MA组与癫痫组相比,神经元损伤明显减轻;丙戊酸钠联合3MA组与丙戊酸钠组相比,神经元损伤明显减轻。免疫组织化学染色、Western Blot、Real-time PCR检测显示,对照组LC3呈低表达,癫痫组LC3表达明显高于对照组;丙戊酸钠组LC3表达明显高于癫痫组;3MA组LC3表达明显低于癫痫组;丙戊酸钠联合3MA组LC3表达明显低于丙戊酸钠组。结论:VPA处理能够诱导癫痫大鼠海马内细胞自噬增加和导致神经元损伤。
Objective: To study the effect of VPA on autophagy, EEG and behavior in hippocampus of epileptic rats. Methods: The epilepsy rat model was made and randomly divided into epilepsy group, 3 methyladenine (3MA) group, VPA group and VPA combined with 3MA group. Normal rats were used as the control group. The changes of behavior and electroencephalogram (EEG) were observed in each group. The damage of neurons was detected by HE and Nissl staining. The expression of autophagy marker microtubule-associated protein 1 light chain 3 (LC3) was detected by immunohistochemistry, Western Blot and real- expression. Results: Behavioral observation and electroencephalogram showed that the combination of sodium valproate and sodium valproate combined with 3MA group can reduce the level of seizure, 3MA group without antiepileptic effect. HE and Nissl staining showed that there was no obvious abnormality in the control group, and the neurons in the epilepsy group were severely damaged. Compared with the epilepsy group, the neuronal damage was significantly reduced in the valproate group. Compared with the epilepsy group, the neuronal damage was significantly reduced in the 3MA group Compared with sodium valproate group, sodium valproate combined with 3MA group significantly reduced neuronal damage. The expression of LC3 in epilepsy group was significantly higher than that in control group by immunohistochemistry, Western Blot and Real-time PCR. The expression of LC3 in sodium valproate group was significantly higher than that in epilepsy group. The expression of LC3 in 3MA group was significantly higher than that in epilepsy group Lower than epilepsy group; LC3 expression in sodium valproate combined with 3MA group was significantly lower than sodium valproate group. Conclusion: VPA treatment can induce the autophagy in hippocampus of epileptic rats and lead to neuronal damage.