基于TLR4/NF-κB/TXNIP/NLRP3信号通路探讨电针预处理调控小胶质细胞极化诱导脑缺血耐受的作用机制

电针预处理可以诱导脑缺血耐受，但其机制尚不明确。我们前期发现电针预处理能抑制TLR4/NF-κB信号通路，缓解炎症反应，诱导脑缺血耐受。最新文献表明，电针预处理能调控小胶质细胞极化对抗神经炎症；TLR4/NF-κB/TXNIP/NLRP3信号通路参与调控小胶质细胞极化过程。我们推测：电针预处理可以抑制TLR4/NF-κB/TXNIP/NLRP3信号通路，调控小胶质细胞极化，对抗神经炎症，诱导脑缺血耐受。本课题通过体内、外实验，观察电针预处理对脑缺血/再灌注后TLR4/NF-κB/TXNIP/NLRP3信号通路及小胶质细胞极化的影响；验证TLR4介导的NF-κB信号启动是TXNIP/NLRP3炎性通路激活的前提；TXNIP是连接NF-κB介导的NLRP3炎性小体活化的关键桥梁分子。阐明TLR4/NF-κB/TXNIP/NLRP3信号通路是电针预处理调控小胶质细胞极化诱导脑缺血耐受的新途径。

Electroacupuncture pretreatment can induce cerebral ischemic tolerance, but its mechanism is not yet clear. We have previously found that electroacupuncture pretreatment can inhibit the TLR4 / NF-κB signaling pathway, relieve inflammation, and induce cerebral ischemic tolerance. The latest literature indicates that electroacupuncture pretreatment can regulate microglia polarization against neuroinflammation; TLR4 / NF-κB / TXNIP / NLRP3 signaling pathway is involved in regulating microglia polarization. We speculate that electroacupuncture pretreatment can inhibit the TLR4 / NF-κB / TXNIP / NLRP3 signaling pathway, regulate microglia polarization against neuroinflammation, then induce cerebral ischemic tolerance. In this study, we will observe the effects of electroacupuncture pretreatment on TLR4 / NF-κB / TXNIP / NLRP3 signaling pathway and microglia polarization after cerebral ischemia/reperfusion through in vivo and in vitro experiments; confirm that TLR4-mediated NF-κB signal initiation is a prerequisite for activation of the TXNIP / NLRP3 inflammatory pathway; TXNIP is a key bridge molecule that connects NF-κB-mediated NLRP3 inflammasome activation. To elucidate that the TLR4 / NF-κB / TXNIP / NLRP3 signaling pathway is a new pathway for electroacupuncture pretreatment to regulate microglia polarization-induced cerebral ischemic tolerance.