Nfat5通过诱导NLRP6炎性复合体的激活促进脑缺血再灌注损伤的作用及机制研究

炎症反应在脑缺血再灌注损伤的发生中起到重要作用。我们首次证实NLRP6炎性复合体的活化可以加重脑缺血再灌注损伤，而其上游调控机制尚不清楚。Nfat5是体内重要的促炎转录因子之一。通过前期的测序，生物信息学分析，结合现有文献报道和前期研究结果，我们提出：“ Nfat5作为NLRP6炎性复合体活化的正调控因子，可能通过从转录水平直接诱导NLRP6炎性复合体活化，或者通过抑制Nrf2/ARE通路或／和PPAR-gamma/NOXs通路,增加ROS生成进而诱导NLRP6炎性复合体的活化，从而加重脑缺血再灌注损伤”。本项目将离体和在体实验结合，采用siRNA干扰和腺相关病毒AAV过表达技术及其他分子生物学方法，探讨Nfat5对NLRP6炎性复合体活化的正调控作用及其可能的机制。本研究将进一步阐明脑缺血再灌注损伤的发病机制，为脑卒中的防治提供新靶点和新策略。

Inflammatory response plays a vital role in cerebral ischemia/reperfusion(I/R) injury. We first demonstrated that activation of the NLRP6 inflammasome could aggravate cerebral I/R injury, but its upstream regulatory mechanisms remain unclear. Nfat5 is one of the important pro-Inflammatory response plays a vital role in cerebral ischemia/reperfusion(I/R) injury. We first demonstrated that activation of the NLRP6 inflammasome could aggravate cerebral I/R injury, but its upstream regulatory mechanisms remain unclear. Nfat5 is one of the important pro-inflammatory transcription factors in vivo. Based on previous sequencing, bioinformatics analysis, existing literature reports and previous research results, we propose: " As a positive regulator of NLRP6 inflammasome activation，Nfat5 may directly induce NLRP6 inflammasome activation from the transcription level , or through the Nrf2 / ARE pathway or / and the PPAR-gamma / NOXs pathway, promoting the production of ROS，thereby aggravating cerebral I/R injury. "This project uses RNA interference and AVV overexpression techniques, and other molecular biological methods to explore the positive regulation of Nfat5 on the activation of NLRP6 inflammasome and its possible mechanism both in vivo and vitro experiments. This study will further clarify the pathogenesis of cerebral I/R injury and provide new targets and strategies for the prevention and treatment of stroke.