吞噬细胞特异性促炎蛋白S100/Calgranulins与缺血性脑卒中预后关系的前瞻性队列研究

以吞噬细胞特异性分泌为特征的炎症-动脉粥样硬化信号通路在缺血性脑卒中的发生发展中发挥重要作用。已有研究显示，吞噬细胞特异的S100/Calgranulins（S100A8/A9和S100A12）所参与的通路是将炎症与动脉粥样硬化和钙稳态联系起来的新兴通路。我们预研究发现，S100A8/A9与缺血性脑卒中预后存在显著的关联，其参与p38MAPK/ERK-NF-κB信号轴调控炎症-动脉粥样硬化信号通路，处于其下游的S100A12可直接影响NF-κB和细胞因子。鉴此推测，S100A12可能成为预测不良预后风险个体的标志物及治疗干预的靶点。本研究在已建立的队列基础上，探讨血浆S100A12与缺血性脑卒中不良临床结局的关系及其可能的炎症机制并结合以往研究构建风险预测模型。本研究将为S100A12作为缺血性脑卒中不良临床结局标志物以及风险预测提供重要的人群研究证据，为病后治疗和康复策略提供新思路。

Phagocyte-specific inflammation-atherosclerosis signaling pathway plays an important role in the progression of ischemic stroke. It has been shown that phagocyte-specific S100/Calgranulins (S100A8/A9 and S100A12) are involved in a novel pathway that links inflammation with atherosclerosis and calcium homeostasis. Our preliminary study found that S100A8/A9 was significantly associated with the prognosis of ischemic stroke, and S100A8/A9 participated in the p38MAPK/ERK-NF-κB signaling axis to regulate the inflammation-atherosclerosis signaling pathway. S100A12, which was downstream of S100A8/A9, could directly affect NF-κB and cytokines. We hypothesized that S100A12 may be a predictor for poor prognosis and a target for therapeutic intervention. Based on the established cohorts, this study explored the association between plasma S100A12 and adverse clinical outcomes in ischemic stroke, and the possible inflammatory mechanisms, and constructed a risk prediction model in combination with our previous studies. The present study will provide important population-based evidence for S100A12 as a predictor for adverse clinical outcomes of ischemic stroke, and offer new ideas for therapy and rehabilitation strategies.