癫痫与神经递质的失衡密切相关。产生ATP是线粒体重要细胞功能；在颞叶癫痫实验动物中发现，线粒体明显功能障碍。线粒体动力学失衡，导致ATP合成障碍，从而细胞内外抑制性神经递质腺苷水平变化。1型平衡型核苷转运体（ENT1）可双向调节细胞内外腺苷的水平；腺苷水平化，势必造成ENT1功能变化。然而，线粒体动力学失衡调控ENT1参与癫痫的机制不清。前期工作发现癫痫后ENT1水平升高。线粒体动力学失衡是否调控ENT1参与癫痫尚无报道。本项目拟使用线粒体分离动力相关蛋白（Drp1）特异性抑制剂Mdivi-1和构建ENT1慢病毒质粒，观察动物脑电行为及膜片钳监测脑片电生理变化，分子生物学技术检测神经细胞相关分子的表达；观察用Mdivi-1前后ENT1变化；最终比较癫痫和非癫痫患者脑组织中Drp1及ENT1的表达，从从分子信号机制的角度揭示癫痫形成机制，期望为癫痫的防治提供新靶点。

Epilepsy is closely related to the imbalance of the neurotransmitter. ATP generation is one of the important mitochondrial cell function，and mitochondrial dysfunction is found obviously in the temporal lobe epilepsy experimental animals. Mitochondria dynamic imbalance causes ATP synthesis disorder, which affects the level of intracellular and extracellular inhibitory neurotransmitter adenosine.Equilibrative nucleoside transporter-1 (ENT1) bidrectional regulates the level of intracellular and extracellular inhibitory neurotransmitter adenosine. The changes of adenosine level results in the changes of ENT1 function. And yet, specific molecular signaling mechanism of mitochondria dynamic imbalance regulating ENT1 function in epilepsy is not clear. The applicant's preliminary work found an upregulation of ENT1 after epilepsy. There is no literature about mitochondria dynamic imbalance regulating ENT1 leading to epilepsy formation. The project intends to use the specific inhibitor（Mdivi-1） of dynamic related protein（Drp1） and build the ENT1 lentiviral plasmid to observe the rat electroencephalogram (EEG)，behavior, using patch clamp to monitor electrophysiological changes in the brain slice, and detecting related molecular expression in the cells by molecular biology technology. The ENT1 function change will be observed by using Mdivi-1, and the brain Drp1 and ENT1 protein expression will be compared between epilepsy patient and non epilepsy patient. Theapplicant expect to reveal epilepsy mechanisms from the molecular signaling perspective, and provide a new target for the prevention and treatment of epilepsy.