肥大细胞参与了中枢神经系统疾病的病理改变。我们前期研究发现，脑缺血后存在着肥大细胞激活，而肥大细胞缺失能保护缺血性脑损伤引起的神经细胞凋亡，但其具体机制仍不清楚。我们进一步预实验发现，肥大细胞缺失能减少ROS的形成及NFκB的磷酸化，而这可能是IKKβ依赖的。因此，我们假设在缺血性脑损伤中，肥大细胞可能通过IKKβ-NFκB-ROS通路而促进神经细胞的凋亡。在本课题中，我们拟利用肥大细胞、IKKβ基因敲除小鼠，以及细胞共培养等技术，从整体、细胞和分子水平上对以上假设作进一步验证。本课题的完成，将进一步深入认识肥大细胞IKKβ-NFκB-ROS通路在缺血性脑损伤中的作用，并可从抑制肥大细胞活化及其下游信号通路出发，为相关药物用于治疗缺血性脑损伤提供新的思路。

Mast cells are critical regulators of the pathogenesis of the central nervous system diseases, including stroke, multiple sclerosis, traumatic brain injury, and brain tumors. Our previous studies found that the mast cells increased significantly after cerebral ischemia, and the apoptosis of neurons significantly decreased in mast cell-deficient mice versus wild type. However, the exact effects of mast cells, and its mechanisms in ischemic injury of brain remained unclear. According to literature and our preliminary studies, we hypothesize that, when brain ischemia occurred, mast cells lead to excitatory injury of neurons by phosphorylation of IKKβ, which activates NFκB signaling pathway, or enhances SNAP-23 phosphorylation. In this study, gene knock-out mice, cell co-culture, and other techniques will be used to clarify: 1. the exact effects of mast cells on ischemic injury of brain; 2. whether the activation of IKKβ is involved in ischemic injury of neurons induced by mast cells, both in vivo and in vitro; 3. whether the inhibitions effect of IKKβ, through regulation of the mast cells, can relieve the ischemic injury of neurons. Through this study, we possibly find a new target to protect the ischemic injury of brain.