摘要
目的:观察氯喹对戊四氮慢性致痫大鼠海马α-氨基羟甲基异恶唑丙酸(amino-3-hydroxy-5-methylisox-azole-4-propionic acid,AMPA)受体(GluR2)及神经型一氧化氮合酶(nitric oxide synthase,nNOS)表达的影响,探讨氯喹在癫痫发生发展中的作用。方法:30只健康雄性SD大鼠,随机分为3组:对照组(10只)、戊四氮致痫组(10只)、氯喹干预组(10只),观察大鼠行为表现和脑电图的改变。应用Western Blot检测大鼠海马GluR2含量的改变,免疫组化检测nNOS的变化。结果:对照组无癫痫发作,戊四氮致痫组癫痫发作严重(III~Ⅴ级),氯喹干预组痫样发作与戊四氮致痫组相比较轻(Ⅰ~III级,P〈0.05);戊四氮致痫组脑电记录呈频发高幅的痫样波,氯喹干预组痫样波幅低且缓;与对照组相比,癫痫组GluR2表达减弱(P〈0.05),氯喹干预组与对照组比较差异有显著性(P〈0.05);nNOS在戊四氮致痫组表达强,以海马为著,与对照组比较差异有显著性(P〈0.05),氯喹干预组与对照组比较无显著性差异(P〉0.05)。结论:氯喹可以通过调节GluR2的含量和抑制nNOS的表达,表明氯喹可能是预防和治疗癫痫的理想药物。
Objective: To observe the effects of chloroquine on GluR2 and nNOS expressions in hippocampi of rats with epilepsy induced by pentyleneterazole,and to explore the role of chloroquine of epileptogenesis.Methods: Thirty male adult Sprague-Dawley(SD) rats were randomly divided into control group(n=10),pentylenetetrazole(PTZ) group(n=10) and chloroquine intervening group(n=10).The behavior and electroencephalogram(EEG) of rats were observed and recorded.Expression of GluR2 and nNOS in hippocampus was examined with Western-Blot and immunohistochemistry,respectively.Results: The control group showed no seizure activity.Severe seizure activity was observed in PTZ group(III-Ⅴclass)and slight seizure activity(Ⅰ-III class) appeared in chloroquine treated group(P〈0.05);EEG showed high amplitudes with higher rates in PTZ group,low-amplitude and slow oscillatious in chloroquine intervention group.GluR2 level in PTZ group was lower in hippocampus as compared with control group(P〈0.05),while no significant difference between chloroquine intervention group and control group was observed(P〉0.05);expressions of nNOS,especially that in hippocampal area,was higher in PTZ group than in control group(P〈0.05),and significant differences were observed in nNOS expressions between chloroquine intervention group and control group(P〈0.05).Conclusion: Chloroquine could modulate the expressional level of GluR2 and inhibit that of nNOS,which suggests that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2011年第4期428-432,共5页
Chinese Journal of Neuroanatomy
基金
山东省教育厅科技计划资助项目(JO8LG14)
关键词
GLUR2
NNOS
氯喹
戊四氮
癫痫
大鼠
GluR2; nitric oxide synthase; chloroquine; pentylenetetrazole; epilepsy; rat