存活脓毒性心肌病（SIC）患者继发心肌慢性纤维化致远期心血管疾病风险增加，但具体机制不清。SIC小鼠心脏可见心脏巨噬细胞（cMΦ）浸润，cMΦ与心脏内皮细胞（cEC）共培养可诱导内皮间充质转化（EndoMT），伴cEC Notch1及Wnt/β-catenin通路上调。基于此，本项目提出假说：浸润性cMΦ通过协同调控cEC Notch1与Wnt/β-catenin通路启动EndoMT介导远期心肌纤维化。本项目拟建立SIC模型，通过流式细胞术分析单核细胞亚型比例对SIC远期纤维化预测价值；免疫荧光观察cMΦ浸润，检测cEC EndoMT标志物表达；报告基因法观察Notch1和Wnt/β-catenin通路交互作用对cEC EndoMT的影响。本项目有助于深入了解SIC患者心肌抑制—慢性纤维化这一连续过程，加深对脓毒症急慢性器官功能障碍的理解，为远期SIC心肌纤维化治疗提供思路和潜在干预靶点。

Patients surviving from septic cardiomyopathy (SIC) have an increased risk of long-term cardiovascular disease due to chronic myocardial fibrosis, however the specific mechanism is unclear. Cardiac macrophage (cMΦ) infiltration was observed in the heart of SIC mice, endothelial mesenchymal transition (EndoMT) was induced by co-culture of cMΦ with cardiac endothelial cells (cEC) and cEC Notch1 and Wnt/β-catenin pathways were up-regulated meantime. Based on this, we proposes a hypothesis that invasive cMΦ initiates endoMT-mediated myocardial fibrosis by synergistically regulating cEC Notch1 and Wnt/β-catenin pathways. We plan to establish a SIC model to analyze the predictive value of monocyte cell subtype ratio for SIC associated fibrosis by flow cytometry，to observe cMΦ infiltration by immunofluorescence, and to detect cEC EndoMT marker expression. We also plan to investigate interaction between Notch1 and Wnt/β-catenin pathway during cEC EndoMT using report genes. This project will help to understand the myocardial fibrosis process in SIC patients, deepen the understanding of acute and chronic organ dysfunction of sepsis, and provide ideas and potential intervention targets for SIC myocardial fibrosis treatment.