氯喹对癫痫状态下神经元自噬的影响
发布时间：2018-10-16 17:27
【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的损伤死亡情况,研究癫痫状态下神经元的损伤死亡与自噬的关系,探讨氯喹对神经元自噬现象的影响以及氯喹是否具有神经元保护性作用,探讨氯喹缓解癫痫发作的作用机制。方法：24只成年雄性Wistar大鼠随机分为生理盐水对照组、戊四氮致痫组及氯喹干预组。各组分别用生理盐水,戊四氮及氯喹腹腔注射制造动物模型。观察和记录各组大鼠在给药后的行为学表现及脑电图变化。应用HE及NISSL染色方法检测各组大鼠皮层区及海马CA1区神经元的损伤程度和存活数量,通过免疫组织化学染色及Western Blot检测各组大鼠大脑皮层区及海马区自噬标记物微管相关蛋白1轻链3(Microtubule-associated protein1 light chain3,MAP1-LC3)和自噬降解蛋白p62的表达情况。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,大脑皮层及海马区出现神经元的大量损伤(P0.05),LC3-II的表达及LC3-II/LC3-I的比值较对照组表达增高(P0.05),p62较对照组明显降低(P0.05),自噬过度激活；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,神经元的损失明显减轻(P0.05),LC3-II的表达显著升高(P0.05),LC3-II/LC3-I的比值明显升高,p62的表达同时升高(P0.05),自噬过程被抑制。结论：癫痫状态可诱导神经元的损伤死亡,同时可导致神经元自噬的过度激活；氯喹可有效的抑制癫痫发作过程中出现的神经元自噬现象,可减少神经元的死亡,具有缓解癫痫发作的作用。
[Abstract]:Objective: to study the death and injury of neurons in the course of epilepsy induced by pentylenetetrazol (PTZ), and to study the relationship between neuronal death and autophagy in epileptic state. To investigate the effect of chloroquine on neuronal autophagy and the protective effect of chloroquine on neuronal autophagy. Methods: 24 adult male Wistar rats were randomly divided into normal saline control group, pentylenetetrazol induced epilepsy group and chloroquine intervention group. The animal models were made by intraperitoneal injection of normal saline, pentylenetetrazole and chloroquine respectively. The behavior and EEG of rats were observed and recorded. HE and NISSL staining were used to detect the degree of injury and survival of neurons in the cortical and hippocampal CA1 regions of rats in each group. Immunohistochemical staining and Western Blot were used to detect the expression of microtubule-associated protein 1 (Microtubule-associated protein1 light chain3,MAP1-LC3) and autophagy degradation protein p62 in cerebral cortex and hippocampus of rats. Results: in the control group, there were no epileptiform seizures, normal EEG waveform, normal neurons, low autophagy, severe epileptiform seizures in pentylenetetrazol induced epilepsy group, and high frequency and high amplitude epileptic waves recorded by EEG in pentylenetetrazol induced epilepsy group. A large number of neuronal damage occurred in cerebral cortex and hippocampus (P0.05), the expression of LC3-II and the ratio of LC3-II/LC3-I were higher than that of control group (P0.05), p62 was significantly lower than control group (P0.05), autophagy was overactivated, chloroquine intervention group had mild epileptiform attack, compared with pentylenetetrazol induced epilepsy group, EEG recorded a decrease in epileptic waveform, significantly reduced neuronal loss (P0.05), significantly increased the expression of LC3-II (P0.05), significantly increased the ratio of LC3-II/LC3-I, p62 expression increased simultaneously (P0.05), autophagy process was inhibited. Conclusion: epileptic status can induce neuronal injury and death and induce excessive activation of neuronal autophagy. Chloroquine can effectively inhibit neuronal autophagy and reduce neuronal death. It has the function of relieving epileptic seizures.
【学位授予单位】：滨州医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1
本文编号：2275115
[Abstract]:Objective: to study the death and injury of neurons in the course of epilepsy induced by pentylenetetrazol (PTZ), and to study the relationship between neuronal death and autophagy in epileptic state. To investigate the effect of chloroquine on neuronal autophagy and the protective effect of chloroquine on neuronal autophagy. Methods: 24 adult male Wistar rats were randomly divided into normal saline control group, pentylenetetrazol induced epilepsy group and chloroquine intervention group. The animal models were made by intraperitoneal injection of normal saline, pentylenetetrazole and chloroquine respectively. The behavior and EEG of rats were observed and recorded. HE and NISSL staining were used to detect the degree of injury and survival of neurons in the cortical and hippocampal CA1 regions of rats in each group. Immunohistochemical staining and Western Blot were used to detect the expression of microtubule-associated protein 1 (Microtubule-associated protein1 light chain3,MAP1-LC3) and autophagy degradation protein p62 in cerebral cortex and hippocampus of rats. Results: in the control group, there were no epileptiform seizures, normal EEG waveform, normal neurons, low autophagy, severe epileptiform seizures in pentylenetetrazol induced epilepsy group, and high frequency and high amplitude epileptic waves recorded by EEG in pentylenetetrazol induced epilepsy group. A large number of neuronal damage occurred in cerebral cortex and hippocampus (P0.05), the expression of LC3-II and the ratio of LC3-II/LC3-I were higher than that of control group (P0.05), p62 was significantly lower than control group (P0.05), autophagy was overactivated, chloroquine intervention group had mild epileptiform attack, compared with pentylenetetrazol induced epilepsy group, EEG recorded a decrease in epileptic waveform, significantly reduced neuronal loss (P0.05), significantly increased the expression of LC3-II (P0.05), significantly increased the ratio of LC3-II/LC3-I, p62 expression increased simultaneously (P0.05), autophagy process was inhibited. Conclusion: epileptic status can induce neuronal injury and death and induce excessive activation of neuronal autophagy. Chloroquine can effectively inhibit neuronal autophagy and reduce neuronal death. It has the function of relieving epileptic seizures.
【学位授予单位】：滨州医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1
【参考文献】
相关期刊论文 前1条
1 荆丽丽;吴淑华;杨东霞;李扬扬;高向前;;氯喹对戊四氮慢性致痫大鼠海马GluR2及nNOS表达的影响[J];神经解剖学杂志;2011年04期
，本文编号：2275115
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