海马神经细胞活化在戊四氮点燃大鼠癫痫形成过程中的作用

The role of the neuronal activation of hippocamus in epileptogenesis of pentylenetetrazol kindling rat

目的 以核因子ｋＢ／Ｐ６５（ｎｕｃｌｅａｒ ｆａｃｔｏｒ ｋＢ，ＮＦ－ ｋＢ／Ｐ６５）的核转位作为神经细胞活化的标志，观察在戊四氮（ｐｅｎｔｙｌｅｎｅｔｅｔｒａｚｏｌ，ＰＴＺ）点燃大鼠出现惊厥之前．即点燃过程中海马神经细胞ＮＦ－ｋＢ活化在癫痫形成过程中的作用。方法 将大鼠随机分为对照组、非药物干预组、药物干预组（苯巴比妥３０ｍｇ／ｋｇ，腹腔注射，每日一次）。除对照组外均以低于急性致惊剂量的ＰＴＺ（４０ｍｇ／ｋｇ，腹腔注射，每日一次）点燃大鼠，用行为学观察和脑电图确定癫痫存在，免疫组织化学方法检测大鼠癫痫形成过程中不同时间点海马ＣＡ各区和齿状回神经细胞ＮＦ－ｋＢ活化，用图像分析系统分析对照组、非药物干预组和药物干预组三大组间海马神经细胞ＮＦ－ｋＢ活化的差异。结果 非药物于预组大鼠均于１７ｄ～２２ｄ点燃，而药物干预组ＰＴＺ点燃大鼠所需时间明显延长（于３０ｄ～３５ｄ点燃），且行为学惊厥程度和脑电痫样放电明显轻于非药物干预组。非药物干预组大鼠在行为学未出现惊厥，脑电图未出现痫样放电的点燃前潜伏期内，其海马ＣＡ各区、齿状回ＮＦ－ｋＢ活化的阳性神经细胞数明显增加，与对照组相比两者有显著性差异（Ｐ＜０．０５）；药物干预组在与非?

Objective To investigate the role of the activation of hippocampal neurons in epileptogenesis of pentylenetetrazol-kindling rat ,we choose NF-kB/P65 translocation into the nucleus as the main indicator of activa- tion of neurons. Methods pentylenetetrazol (PTZ 40mg/kg intraperitoneal injection ,daily) was used to kindle rats,and the immunohistochemical staining was used to detect the activation of NF-kB in hippocampus. The differ- ence of activation of NF-kB in hippocampus between control group, no-drug group and drug group (phenobarbital 30 mg/kg. ip daily) at different time points during kindling were measured by image analysis system. Results All rats in no-drug group were kindled at 17-22d of PTZ ip, while rats in drug group were kindled at 30-35d of PTZ ip, During PTZ-kindling of rats before the occurrence of spontaneous seizure confirmed by behavior and EEG, at 7d, 10d and 14d ,the number of immunoreactive cells of hippocamus in no-drug group continously increased com- pared with that in control without using PTZ (P <0. 05). The number of immunoreactive cells in drug group de- creased compared with that in no-drug group( P <0. 05). Conclusion The activation of hippocampal neurons may be one kind of mechanism of epileptogenesis in the process of PTZ-kindling rats. Phenobarbital can interfere with this epileptogenesis by inhibiting the activation of NF-kB in hippocampus.