摘要
目的 研究抗痫药丙戊酸钠 (VPA)在不同剂量范围对癫痫发作及脑细胞凋亡的影响。 方法 建立马桑内酯 (CL)急性致痫大鼠模型 ,实验动物分为单纯CL组和 5个VPA预处理组 ,VPA剂量分别为 10 ,15 ,2 0 ,30 ,35mg/kg。均于痫性发作 2 4h后断头取脑 ,用TUNEL法检测CA1区 ,CA2区 ,CA3区 ,门区 ,齿状回 ,丘脑 ,丘脑下部 ,杏仁核 ,额叶皮质 ,小脑的神经细胞凋亡现象。 结果 预注射VPA 10～ 30mg/kg组与单纯CL组相比 ,痫性发作程度及各脑区TUNEL阳性细胞密度随着VPA给药浓度的增加而递减。但预注射VPA 35mg /kg组的痫性发作反而较剧烈 ,凋亡脑细胞密度与单纯CL组大鼠相近。结论 VPA在一定剂量范围内能显著有效地减少痫性发作 ,这种发作强度的减轻与多个脑区凋亡神经细胞密度明显减少相对应 ;但当VPA给药剂量超过一定范围则没有同样效应。
Objective To explore the effect of different dosages ranges of sodium valproate(VPA) on the severity of seizure and degree of neuronal apoptosis. Methods The acute epileptic rat model was induced by coriaria lactone(CL) . Dosages of VPA ranges from 10, 15, 20, 30, 35 mg/kg were preinjected 30 min before CL injection. Detected the apoptosis neurons in CA1, CA2, CA3, CA4 regions, dentate gyrus, thalamus, hypothalamus, amygdaloidal body, frontal cortex, cerebellum by means of TUNEL after model rats seizured in about 24 h. Result Compared with those CL model rats untreated with VPA, the seizure severity and the density of TUNEL positive cells were obviously reduced in the rats treated with VPA which dosages ranges from 10, 15, 20, 30 mg/kg. However, in 35 mg/kg cases seizure severity and density of TUNEL positive cells were higher than other groups. Conclusion VPA as an anticonclusant is efficient to decrease the seizure severity and neuronal apoptosis in certain dosages range, it is important to choose and keep up a correct dosage in treatment.
基金
广州市科委基金资助 (JB0 2 2 0 0 0 2 10 8 0 3 )
关键词
丙戊酸钠
致痫鼠模型
马桑内酯
神经元凋亡
sodium valproate
epileptic rat model
coriaria lactone
neuronal apoptosis
