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目的:比较新型抗癫痫药物左乙拉西坦(LEV)和传统抗癫痫药物苯巴比妥(PB)对青霉素点燃癫痫幼鼠海马CA3区神经元形态及钙调素依赖蛋白激酶Ⅱα(CaMKⅡα)的影响。方法:选出生后20 d健康的SD大鼠(雌雄不限)50只,随机分为青霉素致痫组40只和空白对照组10只,将存活的造模成功大鼠随机分为癫痫对照组(用生理盐水灌胃)、LEV组[300 mg/(kg.d)灌胃]和PB组[30 mg/(kg.d)灌胃]。在用药5周后,HE染色观察海马CA3区神经元形态,免疫组化检测CaMKⅡα的表达。结果:空白对照组大鼠海马CA3区神经元排列密集、规则,而致痫组海马神经元排列紊乱、疏松;癫痫对照组、PB组、LEV组与空白对照组比较CaMKⅡα的表达明显减少,差异有统计学意义。PB组与癫痫对照组比较CaMKⅡα的表达稍减少,但差异无统计学意义。LEV组与PB组比较CaMKⅡα的表达增加,差异有统计学意义。结论:发育期反复惊厥可导致大鼠成年后海马神经细胞损伤,造成海马CA3区CaMKⅡα表达下降,故可推测CaMKⅡα的表达下降可能是反复癫痫发作致认知损害的机制之一;长期使用苯巴比妥可使海马CA3区CaMKⅡα表达下降,而长期使用左乙拉西坦对海马CA3区CaMKⅡα表达的影响较小。
OBJECTIVE: To compare the effects of levodocisol (LEV), a new antiepileptic drug, and phenobarbital, a traditional antiepileptic drug, on the neuronal morphology and the expression of calmodulin-dependent protein kinase Ⅱα (CaMKⅡα) in hippocampal CA3 region of penicillin- Impact. Methods: Fifty healthy male Sprague-Dawley rats were randomly divided into penicillin-induced epilepsy group (n = 40) and blank control group (n = 10). Twenty-five surviving rats were randomly divided into epilepsy control group (Intragastric administration of normal saline), LEV group [intragastric administration of 300 mg / (kg.d)] and PB [30 mg / (kg.d) intragastrically]. Five weeks after treatment, the morphology of hippocampal CA3 neurons was observed by HE staining and the expression of CaMKⅡα was detected by immunohistochemistry. Results: The neurons in hippocampal CA3 region of the blank control group were densely arranged and regular. The hippocampal neurons in the epileptic group were disordered and loosely arranged. Compared with the blank control group, the expression of CaMKⅡα in epilepsy control group, PB group and LEV group was significantly decreased There is statistical significance. Compared with epilepsy control group, the expression of CaMKⅡα in PB group was slightly decreased, but the difference was not statistically significant. Compared with PB group, the expression of CaMKⅡα in LEV group increased, the difference was statistically significant. CONCLUSION: Repeated convulsions in developmental period lead to the damage of hippocampal neurons in adult rats and the decrease of CaMKⅡα expression in hippocampal CA3 region. Therefore, it is speculated that the decreased expression of CaMKⅡα may be one of the mechanisms of recurrent cognitive impairment induced by seizures. Betipa could reduce the expression of CaMKⅡα in CA3 of hippocampus, while prolonged use of levetiracetam had little effect on CaMKⅡα expression in hippocampal CA3 region.