急性心肌梗死后内皮细胞微粒及miR-126调控单核细胞迁移并诱导心肌损伤机制研究

急性心肌梗死（AMI）是伴随内皮损伤，免疫炎症激活，凝血级联反应共同介导的复杂综合征。AMI后组织损伤触发强烈的炎症反应和坏死，其中涉及单核细胞等免疫细胞和可溶性介质的广泛浸润。我们前期研究发现AMI过程中产生微粒，其所含miRNA水平与正常生理状态下循环微粒中miRNA水平有显著差异，但其诱导炎症和组织损伤机制仍不清楚。因此，我们拟提出研究假说：AMI后内皮功能障碍激活内皮细胞MK2信号通路，促进EMPs释放并调控其内含miR-126表达，上调EMPs促炎活性及表面VCAM-1等粘附分子表达。同时，EMPs及内含miR-126通过调节单核细胞ITGB2,PlexinB2等蛋白质和基因转录水平，激活脾脏单核细胞迁移至受损心肌，加重免疫炎症反应和组织坏死。本研究拟从临床观察、细胞学研究和动物模型进行探索，明确AMI后EMPs及其内含miR-126调控脾脏单核细胞迁移至受损心肌中作用机制。

Acute myocardial infarction (AMI) is a complex syndrome mediated by endothelial disfunction, immune inflammatory activation and coagulation cascade. Tissue injury after AMI triggers strong local inflammation and necrosis, which involves extensive infiltration of immune cells such as monocytes and soluble mediators. In our previous study, we found that microparticles were produced during the pathogenesis of AMI, and the level of microRNA contained was also significantly different from that of the circulatory system under normal physiological conditions, but its exact mechanism of induce inflammation and tissue damage was still unclear. We proposed that endothelial dysfunction after AMI promotes the release of EMPs and regulates the expression of miR-126 via activating MK2 signaling pathway, and up-regulate the pro-inflammatory activity of EMPs and the expression of adhesion molecules such as VCAM-1 on its surface. At the same time, EMPs and miR-126 can activate splenic monocytes to migrate to local myocardium and induce immune inflammatory response and tissue necrosis by regulating the transcription levels of ITGB2, PlexinB2 in monocytes. This study aims to analyse from the aspect of clinical observation, cytological research and animal model to explore the possible mechanism of EMPs and miR-126 in regulating spleen monocyte migration to the injured myocardium.