癫痫是严重危害人类健康的常见病。申请者早期研究表明，NKCC1和KCC2通过调节细胞内外氯离子浓度的平衡直接参与了颞叶内侧癫痫的形成。目前对NKCC1和KCC2的调控机制尚不明确。预实验表明，mTOR和SGK1在颞叶内侧癫痫海马中异常表达，抑制mTOR或SGK1可以导致NKCC1及KCC2的表达改变。本项目拟在前期研究的基础上，利用分子生物学和细胞膜片钳技术，从患者、动物模型以及细胞多个层面来探讨（1）mTOR和SGK1表达或功能异常是否是癫痫发生的重要因素；（2）mTOR-SGK1信号传导通路是否是痫性刺激下导致NKCC1和KCC2表达与功能异常的胞内调控机理；（3）阻断mTOR-SGK1-NKCC1/KCC2通路的信号传递是否可以避免细胞内外氯离子浓度失衡，减少痫性放电的发生。研究结果将对了解颞叶内侧癫痫的形成有着重要的意义，将可能为颞叶内侧癫痫的治疗提供新的靶点。

Epilepsy is a common disease threatening human health. In our previous studies，NKCC1 and KCC2 were found to play important roles in pathogenesis of mesial temporal lobe epilepsy (MTLE) by regulating intracellular chloride concentration. However, it is not clear which result in expressional changes of NKCC1 and KCC2. Our pre-experiment suggested that the expression of mTOR and SGK1 were also changed in sclerosed hippocampus of MTLE. Inhibiting mTOR or SGK1 could affect NKCC1 and KCC2 expression. This study is a continuation of previous study. In this study, molecular biological technology method and cell patch clamp will be used in epilepsy patients’ tissues, mice epilepsy models and neuro cells to test following possibility: (1) Whether expressional changes of mTOR and SGK1 are important reasons to ignite seizures; (2) Whether mTOR-SGK1 are the regulator of inducing expressional changes of NKCC1 and KCC2 after the attack of seizure; (3) Whether inhibiting mTOR-SGK1-NKCC1/KCC2 pathway could prevent cells from chloride dyshomeostasis and decrease seizures. The results may help us to illustrate the pathogenesis of MTLE and provide a new therapy target for the treatment of MTLE.