炎症免疫反应在心肌缺血再灌注（IR）损伤中起到重要作用。缺血早期心脏聚集的促炎性M1巨噬细胞和中性粒细胞参与心肌IR损伤。我们研究发现：心肌IR早期巨噬细胞表达Dectin-1，促进其向M1极化和表达中性粒细胞趋化因子，促进中性粒细胞向心脏聚集，共同介导心肌IR损伤。因此，Dectin-1有望成为心肌IR损伤新的治疗靶点。进一步靶点预测和验证发现miR-342-3p负向调控Dectin-1表达，且miR-342转基因小鼠心肌IR后心功能较野生型显著改善，提示miR-342-3p靶向Dectin-1调控巨噬细胞极化参与心肌IR损伤。因此，本课题将继续探索：1）炎症因子调控miR-342-3p表达及其分子机制；2）miR-342-3p靶向Dectin-1调控巨噬细胞极化参与心肌IR损伤及其机制；3）血浆miR-342-3p水平与临床急性心梗相关性。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. Pro-inflammatory M1 macrophages and neutrophils accumulated early and contributed to myocardial IR injury. Our previous studies have shown that: Dectin-1 was highly expressed in the macrophage but not neutrophil in the heart, leading to macrophage polarization towards M1 phenotype and chemokines expression associated with neutrophil recruitment, resulting in myocardial IR injury. Therefore, Dectin-1 may be the novel therapeutic target against myocardial IR injury. By software prediction and validation study, we demonstrated that miR-342-3p negatively regulated Dectin-1 expression, and infarct size (Evans blue/TTC staining) and cardiac function (assessed by echocardiography) were significantly improved in miR-342 transgenic mice after myocardial IR, compared with wild type mice, suggesting that miR-342-3p critically involved in myocardial IR injury by targeting Dectin-1 expression and regulating macrophage polarization. Thus, based on these findings, the present study aimed to further explored: 1) The molecular mechanisms for inflammatory cytokines in regulating miR-342-3p expression; 2) Whether miR-342-3p regulates macrophage polarization through targeting Dectin-1, does it contribute to myocardial IR injury, and the underlying molecular mechanisms. 3) The clinical relevance of plasma miR342-3p in patients with acute myocardial infarction. Lastly, we will examine plasma levels of miR342-3p in patients with acute myocardial infarction, and further explore the relationship between miR342-3p and infarct size assessed by magnetic resonance image (MRI). Our findings will provide new therapeutic target for ischemic heart disease.