戊四氮点燃过程中大鼠海马胶质细胞增生和突触重建的研究

目的探讨戊四氮点燃过程中海马胶质细胞增生及突触重建与慢性癫痫发病机制的关系。方法大鼠随机分为对照组、非药物干预组(戊四氮35mg/kg,腹腔注射,每日一次)和药物干预组(苯巴比妥30mg/kg,戊四氮35mg/kg,均为腹腔注射,每日一次)。采用免疫组织化学方法观察胶质原纤维酸性蛋白(GFAP)和神经细胞粘附分子(NCAM)表达水平。结果非药物干预组大鼠注射戊四氮后在行为学未出现惊厥,脑电图未出现痫性放电的点燃前潜伏期内,出现突触重建和胶质细胞增生,以海马CA3区、门区明显,与对照组比较,有显著性差异(P<0.05);与药物干预组对应时间点比较,亦有显著性差异(P<0.05)。结论大鼠注射戊四氮后引起反应性胶质细胞增生和神经元可塑性改变,可能与形成异常神经元放电环路,最终诱发癫痫发作有关,苯巴比妥可抑制异常神经网络的建立,预防癫痫发生。

Experimental Study of Gliosis and Synaptic Reorganization in Hippocampus during Pentylenetrazol-Kindled Epileptogenesis in Rats

Objective To investigate the relationship between gliosis,or synaptic reorganization and the mechanism of chronic epilepsy induced by pentylenetrazol(PTZ)in rats.Methods Forty-two rats were randomly divided into drug-interfered(intraperitoneal injection of30mg/kg phenobarbital and35mg/kg PTZ,daily),no-drug-interfered(intraperitoneal injection of35mg/kg PTZ,daily)and control groups.The expressions of glial fibrillary acidic protein(GFAP)and neural cell adhesion molecule(NCAM)were determined by immunohistochemical technique in the hippocampi of the rats of each group.Result The reactive gliosis and synaptic plasticity in the CA3and hilar areas of dentate gyrus of hippocampus were found before the occurrence of PTZ-induced seizure confirmed by behavior and EEG in the no-drug-interfered group,and significantly different from those in the control and drug-interfered group(P<0.05).Conclusions The changes in the reactive gliosis and neuronal plasticity in the hippocampus after the injecticn of PTZ are probably related to forming the abnormal discharge circuit,and finally inducing the seizures in rats.Penobarbital can prevent this epileptogenesis by inhibiting the establishment of abnormal nervous net in the hippocampus.