GABA_A受体激动剂和拮抗剂对大鼠梨形皮质、海马Fos表达的影响及其与癫痫发病的关系

Effects of the GABA A receptor Agonist and Antagonist on Fos Expression in Rat Piriform Cortex and Hippocampus and Their Relationship with Epilepsy

为探讨γ－氨基丁酸受体（ＧＡＢＡＡ）与癫痫发病机制之间的关系，应用免疫组化技术结合脑电图就ＧＡＢＡＡ受体激动剂蝇蕈醇对马桑内酯致痫大鼠大脑皮质、海马Ｆｏｓ表达的影响进行研究，并与ＧＡＢＡＡ受体拮抗剂荷包牡丹碱致痫大鼠的Ｆｏｓ表达进行比较。结果显示：侧脑室注射马桑内酯诱发癫痫发作后１ｈ，双侧齿状回颗粒细胞层、海马锥体细胞层及注射侧梨形皮质有大量Ｆｏｓ阳性细胞，对侧梨形皮质未检测到Ｆｏｓ表达；侧脑室注射蝇蕈醇可明显抑制齿状回、海马Ｆｏｓ的表达，但梨状皮质Ｆｏｓ表达未受影响。一侧侧脑室注射荷包牡丹碱诱发癫痫发作后１ｈ，双侧梨状皮质有较强的Ｆｏｓ表达，但齿状回、海马未见表达。脑电图也证实马桑内酯及荷包牡丹碱均能诱发棘慢波、尖慢波，蝇蕈醇则能明显抑制这种痫样放电。结果提示。

In order to investigate the relationship between epileptogenetic mechanism and GABA A receptor, the effect of GABA A receptor agonist (muscimol) on Fos protein expression were studied in cerebral cortex and hippocampus of epileptic rats induced by coriaria lactone (CL) by using immunohistochemical staining, and the Fos expression was compared with that of epileptic rats induced by GABA A receptor antagonist (bicuculline). The results showed that there were a lot of Fos positive cells in bilateral granular cellular layer of dentate gyrus, hippocampal pyramidal cellular layer and piriform cortex of injecting side 1h after seizure induced by injecting CL into the lateral ventricle. Fos expression was not observed in contralateral piriform cortex. Muscimol injected into the lateral ventricle inhibited remarkably Fos expression in the dentate gyrus, hippocampal gyrus, while the piriform cortex was not affected. The stronger Fos expression in bilateral piriform cortex but no expression in the dentate gyrus and hippocampus was observed 1h after seizure induced by bicuculline. The electroencephalogram (EEG) confirmed that CL and bicuculline induced spike, slow complex or sharp, slow complex waves, whereas muscimol inhibited these epileptic discharges. These data suggested that GABA A receptor might play an important role in epileptogenesis.