癫痫是一种严重影响人类健康的慢性神经系统疾病, 约1/3为难治性癫痫，其发病机制尚未完全清楚。我们前期研究发现，在海人酸诱导的癫痫小鼠模型海马组织和颞叶癫痫患者海马硬化样本中，富含半胱氨酸的酸性分泌蛋白类似物1（SPARCL-1）的表达量显著上调；在海马神经元中过表达SPARCL-1可诱导自噬发生；采用自噬抑制剂预处理能够使癫痫小鼠模型痫样放电减少，提示SPARCL-1调控的自噬在癫痫发生发展过程中可能具有重要作用。本项目拟结合细胞、动物模型和临床标本，进一步验证SPARCL-1与癫痫的相关性; 在癫痫细胞模型中干扰或过表达 SPARCL-1，检测自噬相关标记物以及相关基因的表达，筛选并明确SPARCL-1调控自噬的信号通路; 采用自噬抑制剂或靶向沉默自噬关键蛋白抑制自噬，探索SPARCL-1调控自噬在癫痫发生过程中的作用，为阐明癫痫的发生机制和治疗提供新的思路。

Epilepsy is a chronic disease which seriously threats to human health and about 1/3 is drug refractory epilepsy. The pathogenesis of epilepsy still remains not completely understood. We found that expression of the secreted protein acidic and rich in cysteine-like 1 (SPARCL-1) was significantly up-regulated in the hippocampus of the seizures model induced by Kainic acid and as well as in the samples of hippocampus sclerosis of human temporal lobe epilepsy. We further found that overexpression of SPARCL-1 could induce autophagy in neuron, and mice of epileptic model pretreated with the autophagy inhibitor showed decreasing abnormal discharges. Therefore, we hypothesize that SPARCL-1 may regulate the epileptogenesis by modulating autophagy. We will further confirm the correlation between SPARCL-1 and epilepsies by using cell and mice model of epilepsy combining with the clinical samples. Interference or overexpression of SPARCL-1 in the cell model of epilepsy will be used to detect the markers of autophagy and confirm that SPARCL-1 induces autophagy, and then we will clarify the molecular mechanism of SPARCL-1-induced autophagy in epileptogenesis. Furthermore, we will inhibit the autophagy by inhibitors or siRNA to clarify the biological function of SPARCL-1-mediated autophagy in the regulation of epileptogenesis. It may provide a new way to explore the pathogenesis of epilepsy and a new target of treatment for epilepsy.