单核细胞源性P-选择素在缺血性卒中预后中作用及其调控血栓形成机制

血栓形成是导致缺血性卒中发生的主要病理机制。P-选择素介导血小板与白细胞、内皮细胞间相互作用，促进血栓形成。本课题组通过对急性缺血性卒中患者颅脑动脉血栓研究发现，血栓中P-选择素主要表达于单核细胞而非既往报道的血小板和内皮细胞，且与卒中不良预后相关，提示单核细胞表达的P-选择素可能在血栓形成中起关键作用；但其在卒中预后中作用及其调控血栓形成的分子机制尚不清楚。据此，本课题拟1）利用缺血性卒中患者生物学样本分析血浆P-选择素、血栓单核细胞P-选择素与卒中预后的关系；2）结合空间转录组和单细胞测序技术筛选血栓中单核细胞高表达P-选择素激活的信号分子和炎症因子表达特征；3）利用小鼠炎症血栓模型和靶向敲除单核细胞源性P-选择素，借助分子生物学技术深入探讨单核细胞源性P-选择素在血栓形成中的作用及相关分子信号途径。成果将丰富人们对P-选择素在炎症血栓中的认识，同时为缺血性卒中治疗新靶点提供实验依据。

Thrombosis is the mainly pathologic mechanism that cause ischemic stroke. P-selectin mediates the interaction between platelets, leukocytes and endothelial cells, which promoting thrombosis. We found that P-selectin in thrombus retrieved from occluded cerebral vessel of patients with acute ischemic stroke, was mainly expressed in monocytes instead of platelets and endothelial cells as previously reported; Meanwhile, thrombus P-selectin was found to be related with poor outcome of stroke, suggesting P-selectin expressed by monocyte may play a key role in thrombosis. However, its role in stroke prognosis and its regulatory mechanism of thrombosis are unknown. Therefore, we intend to 1) analyze the association of serum P-selectin or monocyte-derived P-selectin in thrombus with stroke prognosis using biological samples from acute ischemic stroke patients; 2) screen the molecule signals and inflammatory factors activated by monocyte P-selectin in thrombus using spatial transcriptome technology and single cell sequencing; 3) utilize established inflammatory thrombosis mouse models combining with monocyte-derived P-selectin knockdown to further explore the role and related molecular mechanisms of monocyte-derived P-selectin in thrombosis. The results will enrich our understanding of P-selectin in inflammatory thrombosis and provide experimental evidence for new targets of the treatment in ischemic stroke.