戊四氮致痫大鼠海马c-FOS蛋白表达及钙拮抗剂的影响

C-Fos expression in the hippocampus of rats with pentylenetetrazol-induced epilepsy

目的 :探讨戊四氮 (PTZ)致痫后大鼠的海马锥体细胞、齿状回颗粒细胞 c- FOS蛋白表达情况 ,和钙拮抗剂尼莫地平对 c- FOS蛋白表达的影响。方法 :大鼠腹腔注射 PTZ6 0 mg/ kg建立急性癫痫动物模型 ,测定痫性发作潜伏期、发作强度 ,用免疫组化 L SAB法检测 2 h和 4 h后 c- FOS的表达。结果 :对照组大鼠无癫痫发作 ,干预组痫性发作潜伏期较致痫组明显延长 (P<0 .0 1) ,且发作强度明显减弱 (P<0 .0 1) ;对照组海马各区 c- FOS仅低水平表达 ,致痫后表达明显增高 (P<0 .0 1) ,干预组 2 h比致痫组 2 h的 c- FOS阳性率明显降低 (P<0 .0 1) ,4 h干预组与致痫组无显著性差异 (P>0 .0 5 )。结论 :大剂量 PTZ可诱发大鼠全面阵挛发作 ,诱导海马锥体细胞、齿状回颗粒细胞 c- FOS表达增高 ,海马结构涉及 PTZ致痫引起阵挛发作的发展或传播的病理生理机制 ,尼莫地平可延缓癫痫的发生 ,减轻发作强度 ,降低 c- FOS的表达。

Objective: To investigate the expression of c FOS oncogene in rats hippocampus with pentylenetetrazol(PTZ) induced generalized seizure.To also investigate the anticonvulsant effect of calcium antagonists. Methods: 52 rats was divided into 6 groups,12 received 0.9% saline as control,21 received PTZ, and 19 received both Nimodipine and PTZ. PTZ was injected intraperitoneally and the time to onset of seizure occurrence was recorded. The seizure events were scored using the Racine scale(1972).The c FOS protein expression was observed at 2 h or 4 h using peroxidase labelled streptavidin biotin(LSAB) staining techniques. Results: Control animals had no seizure activity. There was a significant increase in the time to onset of seizure activity in the Nimodi pine treated group, compared with that of the PTZ group ( P <0.01). Seizure activities was more severe in the PTZ group compared with rats who received both PTZ and Nimodipine ( P <0.01). There was low level c FOS protein expression in hippocampal pyramidal neurons and granule cells of the dentate gyrus. C Fos expression was upregulated at the 2nd and 4th hour post PTZ injection. Nimodipine could reduce c FOS protein expression induced by the PTZ induced generalized seizure at 2nd hour post PTZ injection ( P <0.01). There was no significant difference in c FOS expression between the PTZ group and the Nimodipine treated group by 4th hour( P >0.05). Conclusions: PTZ can induce generalized seizure in rat. There is post ictal upregulation of c FOS protein expression in the hippocampal pyramidal neurons and dentate gyrus granule cells. Thus the hippocampus pathways are likely involved in the occurrence of PTZ induced epilepsy. Nimodipine may attenuate PTZ induced seizure activity.