小胶质细胞的大量增殖和炎症因子的释放是脑缺血再灌注损伤的主要机制之一。我们的既有工作表明百日咳毒素（PTx）可抑制自身免疫性脑脊髓炎小鼠模型中小胶质细胞的数量和神经毒性，且预实验提示PTx也可抑制脑缺血后小胶质细胞的激活，但具体机制不清。文献报道，PTx可显著降低血管平滑肌细胞CX3CR1的表达，而我们已证实敲除CX3CR1可有效降低脑缺血后小胶质细胞的增殖和神经毒性。据此，我们推测：PTx可调节脑缺血后小胶质细胞 CX3CR1的表达，继而调节小胶质细胞的增殖和神经毒性,其机制可能是抑制CX3CR1 mRNA合成和增加蛋白降解。我们拟制备中风小鼠模型及细胞缺血模型，分别在体内和体外观察PTx对小胶质细胞的影响，重点关注PTx是否通过NF-kB和STAT1/3来调节CX3CR1的表达。本课题首次在细胞和整体水平，探讨PTx对脑缺血后小胶质细胞的作用及机制，为缺血性脑中风的治疗提供新思路。

Proliferation and releasing inflammatory cytokine of microglia is a main mechanisms of cerebral ischemia reperfusion injury. We have found that pertussis toxin(PTx) can inhibit the proliferation and neurotoxin of microglia in experimental autoimmune encephalomyelitis mice model. Our preliminary experiment also found that PTx can inhibit activation of microglia after cerebral ischemic stroke, but the mechanism is unclear. Others reported that PTx can downregulate CX3CR1 expression of smooth muscle cells significantly, and our published work showed that deficiency of CX3CR1 can suppress activation and neurotoxicity of microglia in ischemic stroke. Therefore, we hypothesize that PTx can regulate the CX3CR1 expression of microglia, then influence the proliferation and neurotoxin of microglia. The mechanism may be that PTx regulate the mRNA expression and degradation of CX3CR1. In this study, we will induce mice middle cerebral artery occlusion (MCAO) model and microglia ischemia model (oxygen and glucose deprivation, OGD)，exploring the role and mechanism of PTx on microglia. We will focus on if PTx regulates the expression of CX3CR1 via NF-kB and STAT1/3 singal pathway? It’s the first time to study the effect and mechanism of PTx in ischemic stroke, this will be a new therapeutic target for ischemia stroke.