神经精神性狼疮(NPSLE)癫痫是SLE危象之一，预后差，易复发。我们前期研究发现NMDA受体表达上调可能是NPSLE重要的致痫原因。因NMDA受体阻滞剂有严重副作用，我们另辟蹊径，从直接阻断NMDA受体转向研究如何调节NMDA受体及其信号传导。我们预实验发现NPSLE癫痫小鼠肥大细胞、组胺、NMDA受体在海马区表达升高，而肥大细胞敲除的NPSLE小鼠癫痫症状减轻。据此我们推测肥大细胞可能通过组胺及其受体在海马区调控NMDA受体继而影响神经元放电，参与NPSLE癫痫发病，肥大细胞或是治疗NPSLE癫痫的一个新靶点。本项目拟先通过临床研究，确认肥大细胞与NPSLE癫痫的相关性，再借助肥大细胞敲除的NPSLE小鼠癫痫模型及肥大细胞与海马神经元共培养等体内体外实验，验证肥大细胞在NPSLE癫痫中的作用并进一步研究其调控NMDA受体的机制。该项目的执行能为NPSLE癫痫的治疗和药物设计提供新思路。

Neuropsychiatric systemic lupus erythematosus (NPSLE) epilepsy is one of the lupus crisis with poor prognosis, tending to recrudesce. Our previous study found that the increase of NMDA receptor maybe one of the important causes of epilepsy in NPSLE. In consideration of severe side effects of NMDA receptor inhibitors, we find a new path to study how to regulate NMDA receptor and its signal transduction instead of directly blocking NMDA receptor. Our pre-experiment results showed that the expressions of mast cells, histamine and NMDA receptor were all increasing in the hippocampal area of NPSLE mice with seizure disorders, and the symptom of epilepsy was alleviated in the NPSLE mice with mast cells knockout. We assume that mast cells could regulate NMDA receptors via histamine and its receptors, leading to neuronal discharge in hippocampal area in NPSLE. Mast cells maybe a new therapeutic target in epilepsy of NPSLE. The following study will confirm the relationship between mast cells and NPSLE epilepsy in clinical research, verify the role of mast cells in NPSLE epilepsy and explore the potential regulating mechanism by using the mast cell-knockout NPSLE mice model and mast cell and hippocampal neuron cells co-culture technique. This research is believed to suggest a new therapeutic approach for NPSLE seizure disorders.