杏仁核注射KA诱导的边缘叶发作致海马神经元凋亡及黄芩苷干预研究  

Effect of bacailin on neuronal apoptosis induced by limbic seizure following kainic acid injection into amygdaloid nucleus

作　　者：李天富[1] 罗玉敏[1] 吕传真[1] 

机构地区：[1]复旦大学医学院华山医院神经科,上海200040

出　　处：《中国神经科学杂志》2003年第6期395-400,共6页

基　　金：卫生部重点基金项目资助 (2 0 0 1 2 0 0 4)

摘　　要：目的 :建立杏仁核注射红藻氨酸 (kainicacid ,KA)诱导的大鼠边缘叶发作模型 ,检测特异性脑电活动和脑血流与海马神经元凋亡的关系 ,以及黄芩苷对神经元损伤的保护作用。 方法 :采用脑立体定位注射技术 ,杏仁核注射KA诱导癫痫发作 ,以深部电极持续记录脑电和激光多普勒血流测定仪记录局部脑血流 (regionalcerebralbloodflow ,r CBF) ,发作 1h后静脉注射 30mg/kg安定终止发作 ,TUNEL染色观察应用黄芩苷和非用药组海马神经元的变化。结果 :药物注射 15～ 2 0min后动物均有癫痫发作 ,脑电图有高频高波伏丛集棘波 ,发作终止 8h时 ,同侧海马CA3区出现TUNEL染色阳性细胞 ,2 4h达高峰 ,72h下降。黄芩苷治疗后TUNEL染色阳性细胞数明显减少。发作前后r CBF无明显变化。高频高波伏丛集棘波时程越长 ,CA3区TUNEL染色阳性细胞越多。结论 :癫痫发作导致选择性海马CA3区神经元凋亡 ,可能与特异性脑电活动有关 ,但与脑缺血无关。黄芩苷对癫痫发作导致的脑损伤有保护作用。Objective: Establishing the focally evoked limbic seizure model to explore the relation between neuronal apoptosis induced by specific pattern of epileptiform activity and regional cerebral blood flow(r-CBF) and to evaluate the protective effect of bacailin on neuronal damage. Methods: Animals received intra-amygdaloid injection of kainic acid (KA) to induce seizure under monitoring with continuous electroencephalographic(EEG) and Laser- Doppler Flowmetry for 1 h,then diazepam (30 mg/kg) was administered to terminate the seizure. The neuronal apoptosis in hippocampus was observed by terminal deoxynucleotidyl transferrase-mediated dUTP nick end labeling (TUNEL) staining in animals with or without bacailin administration. Results: The animals seizured after KA injection 15～20 min and the pattern of seizure activity was characterized by bursts of high frequency polyspike paroxysmal discharges in EEG. TUNEL-positive cells appeared within the ipsilateral CA3 subfield of the hippocampus 8 h after seizure cessation,reached maximal at 24 h and decreased at 72 h. TUNEL-positive cells were significantly decreased in the animals treated with bacailin. The longer the duration of polyspike paroxysmal discharges,the more TUNEL-positive cells appeared in CA3. There was little change in r-CBF after the seizure. Conclusion: KA-induced seizure leads to neuronal apoptosis selectively in CA3 subfield of hippocampus,which may be associated with a specific component of seizure activity electrographically determined,but not related with r-CBF. Bacailin may have protective effect on brain damage induced by seizure.

关 键 词：杏仁核注射 KA 海马 神经元凋亡 黄芩苷 大鼠 红藻氨酸 癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R-33[医药卫生—临床医学]