【摘要】：目的：研究戊四氮誘導大鼠癲癇發(fā)病過程中出現(xiàn)的神經(jīng)元的損傷死亡情況,研究癲癇狀態(tài)下神經(jīng)元的損傷死亡與自噬的關(guān)系,探討氯喹對神經(jīng)元自噬現(xiàn)象的影響以及氯喹是否具有神經(jīng)元保護性作用,探討氯喹緩解癲癇發(fā)作的作用機制。方法：24只成年雄性Wistar大鼠隨機分為生理鹽水對照組、戊四氮致癇組及氯喹干預組。各組分別用生理鹽水,戊四氮及氯喹腹腔注射制造動物模型。觀察和記錄各組大鼠在給藥后的行為學表現(xiàn)及腦電圖變化。應用HE及NISSL染色方法檢測各組大鼠皮層區(qū)及海馬CA1區(qū)神經(jīng)元的損傷程度和存活數(shù)量,通過免疫組織化學染色及Western Blot檢測各組大鼠大腦皮層區(qū)及海馬區(qū)自噬標記物微管相關(guān)蛋白1輕鏈3(Microtubule-associated protein1 light chain3,MAP1-LC3)和自噬降解蛋白p62的表達情況。結(jié)果：對照組無癇樣發(fā)作,腦電圖波形正常,神經(jīng)元處于正常狀態(tài),自噬處于低水平；戊四氮致癇組有重型的癇樣發(fā)作,腦電圖記錄呈高頻高幅的癲癇波形,大腦皮層及海馬區(qū)出現(xiàn)神經(jīng)元的大量損傷(P0.05),LC3-II的表達及LC3-II/LC3-I的比值較對照組表達增高(P0.05),p62較對照組明顯降低(P0.05),自噬過度激活；氯喹干預組有輕型癇樣發(fā)作,與戊四氮致癇組對比,腦電圖記錄癲癇波形減少,神經(jīng)元的損失明顯減輕(P0.05),LC3-II的表達顯著升高(P0.05),LC3-II/LC3-I的比值明顯升高,p62的表達同時升高(P0.05),自噬過程被抑制。結(jié)論：癲癇狀態(tài)可誘導神經(jīng)元的損傷死亡,同時可導致神經(jīng)元自噬的過度激活；氯喹可有效的抑制癲癇發(fā)作過程中出現(xiàn)的神經(jīng)元自噬現(xiàn)象,可減少神經(jīng)元的死亡,具有緩解癲癇發(fā)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.
【學位授予單位】：濱州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R742.1

【參考文獻】

相關(guān)期刊論文 前1條

1 荊麗麗;吳淑華;楊東霞;李揚揚;高向前;;氯喹對戊四氮慢性致癇大鼠海馬GluR2及nNOS表達的影響[J];神經(jīng)解剖學雜志;2011年04期

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本文編號：2275115