兴奋性神经递质，谷氨酸的异常增加是难治性癫痫发生的主要原因。突触间隙的谷氨酸，95%由兴奋性氨基酸转运体（EAAT2）重摄取，EAAT2的表达与功能的损伤可增大癫痫病灶中由过量谷氨酸介导的神经兴奋性或细胞毒性，EAAT2启动子的基因多态性可能会改变EAAT2的表达。本研究通过Taqman real time PCR法测定血中EAAT2启动子的基因多态性；用Western blot 和免疫组化法测定脑组织中EAAT2的蛋白的表达；用HPLC法测定血浆中谷氨酸浓度，建立EAAT2启动子基因多态性与谷氨酸浓度的相关性，用EMSA方法分析基因多态性对转录调控因子与EAAT2启动子结合的影响。本研究对于阐明EAAT2启动子基因多态性导致由兴奋性神经递质异常增加介导的难治性癫痫耐药的机制具有重要的意义。

The abnormal increase of excitatory neurotransmitter glutamate is the main reason for the occurrence of epilepsy. EAAT2 reuptakes 95 percentage of glutamate in the synaptic cleft released from nerve endings, thus terminates the synaptic transmission. The impairment of EAAT2 may cause damage of neurons and glial cells mediated by glutamate. EAAT2 gene polymorphism may change its expression and function, affecting the concentration of glutamate in the brain tissue, resulting in the reported failure of glutamate antagonists in certain patients. This research studies the drug resistant mechanism of refractory epilepsy from the perspective of genetic polymorphisms. First, determine EAAT2 gene polymorphism in blood with Taqman real time PCR method; secondly, measure the concentration of glutamate in blood and by HPLC ; finally, establish the association between gene polymorphism and glutamate concentration in the brain. lastly, EMSA is used to determine the effect of the polymorphism on transcriptional factors binding to the EAAT2 promoter. Therefore, EAAT2 promoter gene polymorphism plays an important role in the drug resistant mechanism of intractable epilepsy mediated by increased glutmate concentration.