红藻氨酸诱导癫痫发作大鼠海马EphA5受体及其配体ephrinA3基因表达变化的研究

Study of the changes of EphA5 receptor and ephrinA3 ligand in hippocampus of rat following kainic acid induced epileptic seizure

目的研究在红藻氨酸(Kainic acid,KA)诱导的损伤型颞叶癫痫(Mesial temporal lobe epilepsy,MTLE)的大鼠海马中,轴突导向因子EphA5受体及其配体ephrinA3基因表达的变化,探讨EphA5/ephrinA3与癫痫后海马兴奋性神经网络形成的作用和关系。方法侧脑室内微量注射KA,建立KA诱导的成年大鼠MTLE模型,用原位杂交法检测癫痫发作1d、1周、2周、3周、4周大鼠海马内EphA5/ephrinA3 mRNA的表达,定量分析表达的动态变化。结果EphA5/ephrinA3 mRNA于癫痫发作后1周,在海马齿状回颗粒细胞层和CA_3区锥体细胞层开始增强,2周达到高峰,4周恢复接近对照组水平。结论在KA所致的癫痫持续状态(Status epilepsy,SE)中,海马神经元通过增强EphA5/ephrinA3 mRNA的表达。调控MTLE大鼠海马内苔藓纤维和突触的重建,是癫痫后海马新的稳定的异常兴奋性神经网络形成的可能机制。

Objective To study the gene expression change of axon guidance factor EphA5 receptor and its ephrinA3 ligand,and explore the effect and relationship with excitatory neural network in hippocampus after mesial temporal lobe epilepsy（MTLE）. Methods Establishing the MTLE model of adult rats following kainic acid（KA） induced epileptic seizure by micro-injection kainic acid in lateral cerebral ventricle. NS control and experimental groups were divided randomly. Observing dynamic change of the expression of EphAS/ephrinA3 mRNA in hippocampus after epileptic seizure at 1d, 1w, 2w, 3w, 4w. In-situ hybridization methods was used,and quantitatively analyse the dynamic movement was detected by computer imaging analytical technique. Results At granular cell layer of dentate gyrus and pyramidal layer of CA3 region in hippocampus,the expression of EphA5/ephrinA3 mRNA began increasing at 1w,at 2w reached the peak,and at 4w was close to control group level. Conclusion The increasing expression of EphA5/ephrinA3 mRNA in hippocampal neuron after KA induced epileptic seizure could regulate mossy fiber sprout and synaptic reconstruction in hippocampus of MTLE rats, which may be possible mechanism of the formation of stable abnormal excitatory neural network after epilepsy.