摘要
目的观察氯喹对戊四氮致痫大鼠皮质和海马谷氨酸(glutamate,Glu)和N-甲基-D-天冬氨酸受体1(NMDAR1,NR1)表达的影响,探讨氯喹在癫痫发生发展过程中对神经递质传导的作用。方法48只健康雄性SD大鼠随机分为对照组(12只)、戊四氮致痫组(60mg/kg,i.p.,18只)和氯喹干预组(0.61mg/kg,i.c.v.,18只)。每组分6个时间点:1h、2h、4h、8h、12h和24h。观察大鼠行为表现和脑电图改变,用免疫组化检测大鼠皮质和海马Glu和NR1的变化。结果对照组无痫样发作,戊四氮致痫组有重型的痫样发作(Ⅲ-Ⅴ级),氯喹干预组有轻型的痫样发作(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;Glu和NR1在戊四氮致痫组表达强,以海马为著,与对照组比较有显著性差异(P<0.05),氯喹干预组与对照组比较无显著性差异(P>0.05)。结论氯喹通过对戊四氮致痫大鼠皮质和海马神经递质Glu和NR1信号传导通路的抑制作用,影响致痫大鼠痫样发作的发生和发展。
Objective To observe the effects of chloroquine on the expressions of glutamate （Glu） and N-methyl-D-asperate receptor 1 （NMDAR1, NR1） in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole （PTZ）, and to explore the role of chloroquine in the epileptogenesis and development process. Methods Forty-eight male adult SD rats were randomly divided into the control group （n=12）, PTZ group （60mg/kg, i. p, n= 18） and chloroquine intervening group （0. 61mg/kg, i. c. v. , n=18）. Each group was further classified into lh, 2h, 4h, 8h, 12h, and 24h subgroups. The behavior and EEG of rats were observed and recorded. The expressions of Glu and NR1 in hippocampus and cerebral cortex were demonstrated with immunohistochemistry. Results The control group showed no seizure activity. Severe seizure activity was observed in the PTZ group （Ⅳ-Ⅴ class）, but slight seizure activity （ Ⅰ-Ⅲ class） appeared in the chloroquine intervening group （P〈0. 05）. EEG showed that there were high amplitudes with higher rates in the PTZ group, but slow oscillations in the chloroquine intervening group. The expressions of Glu and NR1 were stronger in the PTZ group than those of the control group, especially in the hippocampal area （P〈0. 05）. There were no differences in the expressions of Glu and NR1 between chloroquine intervening and control groups. Conclusion Chloroquine, by inhibiting the signal transductation of Glu and NR1 in hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.
出处
《中国组织化学与细胞化学杂志》
CAS
CSCD
2006年第1期18-23,共6页
Chinese Journal of Histochemistry and Cytochemistry
基金
国家自然科学基金重点项目资助(No.30230140)
