干预心肌微环境中巨噬细胞M2型极化被认为是极具应用前景的治疗心肌梗死的新策略，但其调控机制远未阐明，也未见基于促进巨噬细胞M2极化治疗心肌梗死的小分子化合物的报道。我们前期研究发现，新型小分子化合物YLF466D可促进巨噬细胞的M2型极化，从而对心肌梗死发挥极为显著的治疗作用， AMPKα1及转录因子C/EBPβ和HIF-1α可能参与了这一过程。基于此，本课题将研究YLF466D通过促进M2型极化发挥心肌保护作用的可能机制；阐明YLF466D激活AMPKα1的分子机制及其在促进M2型极化中的作用地位；揭示YLF466D作用下，AMPKα1激活对C/EBPβ与HIF-1α及其下游靶蛋白的调控作用。本课题将发现具有调控心脏巨噬细胞M2型极化的新型化合物，阐明其调控M2型极化的新分子机制，确证通过小分子化合物干预M2型极化治疗心肌梗死的可行性，为设计新型治疗心肌梗死的化合物提供新思路。

Mediation of the M2 polarization of macrophages in micro-environment of cardiomyocytes is considered to be a promising strategy for the therapy of myocardial infarction (MI). However, the molecular mechanism involved in M2 polarization is far from being elucidated, and the development of small molecule compounds that can interfere the M2 polarization is still in its early stage. Our previous studies have found that YLF466D, an active monomer compound with new structure, significantly promotes the M2 polarization of macrophages, and effectively protects cardiomyocytes from MI. AMPKα1 kinase and transcriptional factors C/EBPβ and HIF-1α might play an important role in this process. Based on these previous studies, we will further investigate the cardio-protective effect of YLF466D resulted from M2 polarization of macrophages. We will also study the role of AMPKα1 in YLF466D induced M2 polarization, and elucidate the underlying mechanisms of AMPKα1 mediated up-regulation of C/EBPβ and HIF-1α. Our study will not only discover a new compound that can specifically promote the M2 polarization of macrophages, but also enhance our understanding of the molecular mechanisms involved in M2 polarization. Moreover, our study will confirm the feasibility of anti-MI strategies targeting macrophage polarization by small molecule compounds and provide potential therapeutic targets for MI therapy.