难治性癫痫持续状态(RSE)为神经科急症，致死致残率极高，治疗棘手。既往研究表明炎症在癫痫持续状态(SE)的启动及维持中扮演了重要角色，即存在炎症→SE→炎症→RSE这一恶性循环，但在这恶性循环中扮演关键角色的调控分子并不清楚。我课题组最新实验发现在大鼠SE模型早期(5分钟)降钙素原(PCT)大量产生，增高幅度明显强于CRP与IL1等，尤以海马部位表现突出，且PCT可以明显提高神经元兴奋性并下调膜表面抑制性受体的表达，提示：PCT可能是RSE发生中的关键靶点分子。本项目拟在前期研究基础上，采用我们建立的脂多糖诱导RSE动物模型，首先观察该模型海马PCT的时空表达特征；进而探索PCT对神经元兴奋性与抑制性受体膜转运及电生理特性的影响，对胶质细胞炎性状态的作用；进一步鉴定PCT可能的受体及下游信号通路；最后调控海马PCT的表达，观察对RSE的治疗效果。本项目的完成将为RSE的治疗提供新的靶点。

Refractory Status Epilepticus (RSE) is an intractable neurological emergency, with high lethality and disability rate. The previous studies suggest that inflammation plays a critical role on the initiation and maintenance of status epilepticus (SE), which means that there is an vicious cycle, inflammation→SE→inflammation→RSE. However, the key regulatory molecules involved in the vicious cycle remain unclear. Recently, we found that PCT levels in SE rats model were significantly elevated at the very early stage (5 min post SE), especially in the hippocampus. The increased level of PCT was remarkably higher than that of CRP, IL1, and etc. In addition, our preliminary in vitro studies showed that PCT can reduce the cell surface expression of GABAA receptors and increase the excitability of CA1 pyramidal neurons. These results suggest that PCT might be a key targeting molecule for RSE. Based on the preliminary work, we will seek to clarify the role of hippocampal PCT in the pathophysiological mechanism of RSE. Firstly, we will examine the spatio-temporal expression profile of PCT in the hippocampus of our established LPS-induced RSE model. Then, we will explore the effects of PCT on the trafficking of neuronal excitatory and inhibitory receptors, the electrophysiological properties, and the inflammatory state of glial cells. We will further identify the interacting receptor of PCT and the signaling pathway. Finally, we will investigate the treatment effects of regulating the expression of PCT in the rat hippocampus on RSE. Our study will provide a new therapeutic target for RSE.