拉莫三嗪联合尼莫地平对癫痫大鼠海马CA_3区神经元的影响

Effects of Lamotrogine and Nimotopine on Neurons in Hippocampal CA_3 area of Coriaria Lactone-induced Seizure in Rats

目的采用尼莫地平单药及联合拉莫三嗪用药观察马桑内酯(coriaria lactone,CL)致痫大鼠海马CA3区神经元凋亡和P53蛋白表达的变化,了解神经元凋亡及P53蛋白表达与急性癫痫之间的关系,探讨离子通道阻滞剂在抗癫痫治疗中最佳联合用药方案。方法成年雄性SD大鼠50只,随机分为对照组、模型组和治疗组,采用马桑内酯(50μg/kg)侧脑室注射法建立急性癫痫动物模型。治疗组分别给与尼莫地平、拉莫三嗪以及尼莫地平联合拉莫三嗪治疗后应用原位末端标记(TUNEL)和辣根过氧化物酶标记链霉卵白素生物素法测定海马CA3区神经元凋亡与P53蛋白的表达。结果与尼莫地平组和拉莫三嗪组比较,联合治疗组海马CA3区P53阳性细胞数和TUNEL染色凋亡细胞数均显著减少(P<0.05)。结论尼莫地平与拉莫三嗪联合用药对马桑内酯致痫后海马CA3区神经元凋亡和P53蛋白表达有抑制作用,优于单药组,可能对痫性发作引起的神经元凋亡有保护作用。

Objective To investigate the effects of nimotopine（NTP）, lamotrigine（LTG） and combined using of them on neuronal apoptosis and the expression of P53 protein in hippocanmpal CA3 region of the rats with coriaria lactone-induced epilepsy and to explore the best method among antiepileptic treatment.Methods 50 adult male Sprague-Dawley rats were divided randomly into control group,model group and treat group.The rats of model group and treat group were injected coriaria lactone（50 μg/kg） into lateral ventricle（LV） to establish acute rat seizure model.After the treatment of NTP,LTG and combined using of them,neuronal apoptosis and the expression of P53 protein were identified by terminal deoxynucletidy transerase-mediated dUTP-biotin in situ nick end labeling（TUNEL） assay and immunohistochemical staining.Results Compared with NTP treat group and LTG treat group,the numbers of P53 positive cells and apoptosis cells of combined treat group were all significantly decreased（P0.05）.Conclusion Combination of NTP and LTG can effectively restrain the expression of P53 protein and neuronal apoptosis of hippocampus after coriaria lactone-induced epilepsy, and has neuroprotective effects on neuronal apoptosis induced by epilepsy.