小胶质细胞过度激活是颅脑爆震伤（bTBI）继发缺氧损伤引起神经炎症反应的标志性事件，但其机制尚未阐明。钾通道MaxiK是细胞感知缺氧的重要通道蛋白。我们前期发现MaxiK激活可诱发神经炎症反应，其特异性阻断剂可降低bTBI大鼠脑组织IL-1β等炎症因子水平，改善继发性损伤。已知IL-1β的活性主要受NLRP3炎性小体调控，而钾通道开放引起K+外流是NLRP3激活的重要诱因。据此我们推测，bTBI后缺氧可使MaxiK开放导致NLRP3激活进而介导神经炎症反应的发生。本课题拟采用干扰沉默和抑制剂等手段从细胞、脑片氧糖剥夺模型和大鼠bTBI模型三个层次明确MaxiK在bTBI后神经炎症反应中的作用。在此基础上利用基因沉默、FRET等技术研究MaxiK对NLRP3复合体组装过程及相关信号分子的影响，从而揭示MaxiK激活NLRP3的分子机制。本研究将为bTBI继发性损伤治疗策略的研究提供新思路。

The over- activation of microglia is the hallmark of the neuroinflammation induced by hypoxia after blast- induced traumatic brain injury (bTBI), but little is known about the detailed mechanism. MaxiK is the most significant channel protein in cell apperception the hypoxia circumstances. In previous work we have found, for the first time, that the neuroinflammation can be induced by the activation of MaxiK, and the blocker of MaxiK could decrease the level of IL-1β in cortex and attenuate the secondary injury in bTBI rats. What’s known is that the activity of IL-1β is regulated by NLRP3 inflammasome. Meanwhile, K+ efflux is the significant upstream of NLRP3 activation. Base on the findings above, a hypothesis was proposed that MaxiK channel may activate the NLRP3 inflammasome in neuroinflammatory response induced by hypoxia after bTBI. In present study, the effect of MaxiK in the neuroinflammation after bTBI will be investigated in oxygen glucose deprivation (OGD) cell and cortex brain- slice, and in the bTBI rats using RNA interference and blocker of MaxiK. Furthermore, we will identify the roles of MaxiK- triggered NLRP3 activation in the assembly of inflammasome multi-proteins complex and expression of NLRP3 using fluorescence resonance energy transfer (FRET), RNA interference and other techniques to reveal the molecular mechanism of MaxiK activating NLRP3. This study will bring new insight into the development of novel therapeutics that target the secondary injury of bTBI.