神经细胞自噬水平下降在创伤后癫痫易患性增加中的作用及机制研究

Post-traumatic epilepsy is the main reason of epilepsy in young people. The pathophysiological changes in latent period of PTE can increase the risk of PTE, while the mechanism in unclear. Our previous study demonstrated that nerve autophagy decreased in trauma rats, the brain increased sensitivity to noxious stimulation, and the six possible associated cytokines were screened out, while the role and the mechanism of which is unclear. Our study aims at exploring the rule of time sequence of autophagy and cytokines in the latent period of post-traumatic epilepsy, observing the incidence of post-traumatic epilepsy through molecular biology, morphology and pharmacological intervention methods. At the cellular level，our goal is to discuss the role and mechanism of trauma-related cytokines in nerve autophagy and nerve cell survival through gene transfection and interference methods, in order to look for the serum cytokines associated with autophagy and clarify the role and significance of cytokines in the process of PTE, which could provide the basis for clinical predict the occurrence of PTE.

创伤后癫痫（PTE）是青年人癫痫发病的主要原因，PTE潜伏期内的神经生物学改变可增加PTE发生的风险，但其机制尚不明确。我们前期原创性研究发现，PTE潜伏期内神经细胞自噬水平下降，脑组织对皮层下注射FeCl2损伤刺激的敏感性增加，以及与损伤相关的6种炎性细胞因子释放增多，但其机制和意义不清。本研究拟通过制备PTE大鼠模型，运用分子生物学、形态学及药理学干预等手段，动态观察创伤后神经细胞自噬水平的变化及创伤后癫痫发生率，探讨神经细胞自噬水平下降的时间规律及意义；在细胞水平，利用基因转染、基因干扰及药理学干预等方法，探讨创伤后早期筛选出的6种细胞因子对培养的神经元细胞自噬水平及细胞存活的影响，以寻找创伤后血清中与自噬下降有关的细胞因子，明确其在PTE发生过程中的作用及机制。本课题从PTE潜伏期自噬水平下降的角度探讨PTE发生的早期机制，并寻找早期的预警分子，为临床预测PTE发生提供理论依据。