TIM-1+ Bregs细胞在心肌缺血再灌注损伤中的作用机制研究

心肌缺血再灌注损伤是心肌缺血后出现的严重并发症。课题组前期研究发现TIM-1单克隆抗体RMT1-10可以有效保护心肌缺血再灌注损伤，但机制不清。最新研究发现TIM-1主要在表达IL-10的调节性B细胞（Bregs）上高表达，是IL-10+ Bregs的标志物。进一步研究发现心肌缺血再灌注损伤区TIM-1+ Bregs细胞短暂增多，但RMT1-10干预组TIM-1+ Bregs数量和IL-10分泌显著增加，而TIM-1+ Bregs在其中的机制并不清楚。本项目拟利用全光谱流式细胞分析和Luminex多因子检测，探索TIM-1+ Bregs在心肌缺血再灌注损伤中的免疫调控作用，并联合RNA-seq转录组测序，揭示RMT1-10增加TIM-1+ Bregs和IL-10的分子机制。本项目的顺利实施可以丰富心肌缺血再灌注损伤中的免疫调控理论，为以TIM-1为靶点治疗心肌缺血再灌注损伤提供理论依据。

Myocardial ischemia-reperfusion injury is a serious complication after myocardium ischemia. Previously, we discovered that early intervention with RMT1-10 (TIM-1 monoclonal antibody) can effectively protect myocardium from reperfusion injury. However, the underlining mechanisms need further unveiling. Recent study proved that TIM-1 overexpression is mainly seen in regulatory B cells (Bregs) expressing IL-10 and Tim-1 is a marker of IL-10 + Bregs. Further, we found that the number of TIM-1+ Bregs cells increased temporarily in the myocardial ischemia-reperfusion injury region and the number of TIM-1+ Bregs and IL-10 secretion increased significantly in the RMT1-10 intervention group. However, the specific role and mechanism of TIM-1+ Bregs in myocardial ischemia-reperfusion injury are not clear. In the present study, we hope to investigate the role of TIM-1+ Bregs in myocardial ischemia-reperfusion injury by using full-spectrum flow cytometry (FCM) and Luminex multifactor assay. We also hope to reveal the molecular mechanism of RMT1-10 on increasing the number of TIM-1+ Bregs cells and the secretion of IL-10 with the help of sequencing RNA-seq transcriptome. This study can enrich the theory of immunoinflammation regulation in myocardial ischemia-reperfusion injury, and provide theoretical basis for TIM-1 target treatment of myocardial ischemia-reperfusion injury.