XBP1/GABBR1信号轴通过调控Ca2+对癫痫中神经元的保护作用及其机制研究

神经元丢失是癫痫发生的关键因素之一，而神经元凋亡是其重要形式。我们前期发现内质网应激明星因子XBP1在癫痫中高表达，过表达XBP1可降低癫痫中神经元凋亡率以及影响相关凋亡蛋白的表达，并且XBP1可与癫痫基因标志物GABBR1直接结合，GABBR1可增强XBP1在癫痫中对神经元的保护作用，我们推测XBP1/GABBR1可能是一条可调控癫痫发展的新型信号轴。而XBP1/GABBR1轴可能通过正调控钙通道蛋白CALB1减少Ca2+内流，从而抑制神经元凋亡减少，对抗癫痫发展。为了验证这一假说，本项目拟通过细胞凋亡和钙离子浓度检测等实验阐明XBP1/GABBR1轴在癫痫中的保护作用及其机制，并进行体内、外验证XBP1/GABBR1信号轴是否能缓解癫痫的各项相关指标。若本项目的假说被证实，则将有助于进一步理解癫痫的发病机制，为其防治提供新的切入点。

Neuronal loss is one of the key factors in epileptogenesis, and neuronal apoptosis is an important form. We previously found that ER stress star factor XBP1 is highly expressed in epilepsy, overexpression of XBP1 can reduce the rate of neuronal apoptosis in epilepsy and affect the expression of related apoptotic proteins, and XBP1 can directly bind to the epileptic gene marker GABBR1, which can enhance the protective effect of XBP1 on neurons in epilepsy, and we speculated that XBP1/GABBR1 may be a novel signaling axis that can regulate the development of epilepsy. The XBP1/GABBR1 axis may reduce Ca2 + influx by positively regulating CALB1, thereby inhibiting reduced neuronal apoptosis and on antiepileptic development. In order to test the hypothesis, this project intends to elucidate the protective effect of XBP1/GABBR1 axis in epilepsy and its mechanism by experiments such as apoptosis and calcium concentration detection, and to verify whether XBP1/GABBR1 signaling axis can alleviate various related indicators of epilepsy in vitro and in vivo. If the hypothesis of this project is confirmed, it will help to further understand the pathogenesis of epilepsy and provide a new entry point for its prevention and treatment.