炎症免疫反应在心肌缺血再灌注（IR)损伤起到重要作用。缺血释放的损伤相关模式分子（DAMPs）与模式识别受体（PRRs）结合介导巨噬细胞炎症。我们研究发现：1）心梗后早期聚集心脏的促炎性巨噬细胞表达较高的PRRs-Dectin-1；2）Dectin-1-/-小鼠IR后心梗面积和心功能较野生型显著改善；3）IR后心肌释放的DAMPs-过氧化物酶6（Prdx6）表达显著增高，且与Dectin-1结合，表明Prdx6/Dectin-1轴可能参与心肌IR损伤。因此，本课题将继续探索：1）Prdx6/Dectin-1轴介导髓系细胞炎症反应，释放促炎性因子，进而提高γδT细胞分泌IL-17，协同参与心肌损伤；2）干预Prdx6/Dectin-1轴对心肌IR损伤的作用及其机制；3）血清Prdx6水平、Dectin-1＋髓系细胞与临床急性心肌梗死的相关性。为防治缺血性心脏病提供新的治疗策略和干预靶点。

Mounting evidence suggested that inflammation and immune response play an important role in myocardial ischemia reperfusion (IR) injury. Damage-associated molecular patterns (DAMPs) were released from the ischemic heart, which could trigger macrophage inflammation through binding Pattern recognition receptors (PRRs). Our previous studies have showed that: 1) Dectin-1, one of PRRs, was highly expressed in the pro-inflammatory macrophages (also called M1 macrophages), which were recruited in the early phase after myocardial infarction; 2) We further demonstrated that infarct size (Evans blue/TTC staining) and cardiac function (assessed by echocardiography) were significantly improved in Dectin-1 knockout mice after myocardial IR, compared with wild type mice; 3) We identified a DAMPs-peroxiredoxin 6 (Prdx6) as an endogenous, activating ligand for Dectin-1, which was highly expressed in the heart after cardiac IR. These results indicated that Prdx6/Dectin-1 axis may contribute to cardiac IR injury. Thus, based on these findings, the present study aimed to further explored: 1) Prdx6 promotes inflammatory cytokines expression (such as TNF-α, IL- 1β, IL-6 and IL-23) in myeloid cells (including macrophages and neutrophils) through binding its receptor Dectin-1. And these pro-inflammatory cytokines further promote IL-17 production from γδT cells，and synergistically exaggerate cardiac injury. 2) Intervention of Prdx6/Dectin-1 axis on cardiac IR injury and its mechanisms in vivo. 3) Lastly, we will examine serum levels of Prdx6 and circulating Dectin-1+ myeloid cells in patients with acute myocardial infarction, and further explore the relationship between prdx6/Dectin-1 axis and infarct size assessed by magnetic resonance image (MRI). Our findings will provide new therapeutic target for ischemic heart disease.