氯喹对癫痫大鼠海马区神经元自噬的影响  

The effects of chloroquine on neuronal autophagy in hippocampus of rats with status epilepticus

作　　者：郭翀 吴淑华[2] 朱玉红[2] 李建民[1] 

机构地区：[1]滨州医学院附属医院神经外科,滨州256603 [2]滨州医学院附属医院病理科,滨州256603

出　　处：《神经解剖学杂志》2014年第2期192-196,共5页Chinese Journal of Neuroanatomy

基　　金：山东省教育厅科技计划资助项目(JO8LG14)

摘　　要：目的:研究戊四氮诱导大鼠癫痫发病过程中出现的神经元自噬现象,探讨氯喹对神经元自噬现象的影响,探讨氯喹缓解癫痫的作用机制。方法:Wistar大鼠24只随机分为对照组、戊四氮致痫组及氯喹干预组。观察各组大鼠行为表现和脑电图变化,用HE、Nissl染色检测各组大鼠海马区神经元的损伤程度,应用免疫组化检测各组海马自噬标记物微管相关蛋白l轻链3(LC3)的表达。结果:对照组无痫样发作,脑电图波形正常,神经元处于正常状态,自噬处于低水平;戊四氮致痫组有重型的痫样发作,脑电图记录呈高频高幅的癫痫波形,并且出现神经元的大量死亡(P<0.05),LC3较对照组表达增高(P<0.05);氯喹干预组有轻型痫样发作,与戊四氮致痫组对比,脑电图记录癫痫波形减少,神经元的损伤明显减轻(P<0.05),LC3的表达显著升高(P<0.05),自噬过程被抑制。结论:氯喹可以有效的抑制癫痫发作过程中出现的神经元自噬现象,减少神经元的死亡,从而达到缓解癫痫发作的作用。Objective： To investigate the neuronal autophagy in rat hippocampus with status epilepticus induced by pentamethazol and to probe the effects of chloroquine on neuronal autophagy, and explore the suppressing effects and mecha- nisms of chloroquine in epilepsy process. Methods： 24 adult male Wistar rats were randomly divided into three groups, named as control group, pentamethazol induced epilepsy group and chloroquine pretreatment group. The behavior and e- lectroencephalogram of rats were observed and recorded within 2h after injection. The HE and Nissl staining were used to detect the level of neuronal loss. The level of microtubule-associated protein light chain 3 （ LC3 ） examined by immuno- histochemieal was used to reflect the expression of autophagy. Results： No convulsion was emerged in the control group. Seizure intensity in the pentamethazol group was more severe than that in the chloroquine pretreatment group. Electroen- cephalogram recordings from hippocampus showed no epileptic spikes in the control group. There were high amplitudes with fast frequency signals in pentamethazol group, low-amplitude and slow frequency signals in chloroquine group. The HE and Nissl staining results showed that obvious neuronal loss was observed in hippocampus CA1 area in pentamethazol group, the number of survival neuron cells was significantly reduced compared to control group （ P 〈 0.05 ）. The level of LC3 was significantly increased （ P 〈 0.05 ）. Chloroquine remarkably inhibited the process of autophagy and neuronal loss compared to pentamethazol group （ P 〈 0.05 ）. Conclusion： Chloroquine partially inhibited the hyperactivation of autophagy in neurons, playedas a neuroprotective role in rats with status epilepticus induced by pentamethazol, and suppressed seizure to a certain extent, could be a potential antiepileptic drugs.

关 键 词：氯喹 癫痫状态 自噬 神经元损伤 海马 戊四氮 大鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]