最新研究认为有氧康复运动对射血分数保留心力衰竭（HFpEF）患者获益，但其机制不明，临床应用受限。已知心脏巨噬细胞（cMՓ）诱导的心脏纤维化是HFpEF发生发展的重要病理机制。我们发现有氧运动可减少HFpEF小鼠cMՓ的数量及促炎因子表达，同时伴随血清环氧二十碳三烯酸（EETs）浓度升高。前期我们已经证实EETs是有氧运动保护心脏的重要介质，而EETs可抑制巨噬细胞的促炎反应。由此提出“有氧运动通过上调EETs抑制cMՓ，减轻心脏纤维化，从而发挥改善HFpEF作用”的科学假说。为此本研究首先验证EETs介导有氧运动对cMՓ的调控，接着从炎性基因组蛋白去乙酰化层面入手，进一步以STAT6-HDAC3轴为切入点，阐明EETs调控cMՓ的分子机制。本研究旨在为临床上高度关注的“如何有效治疗HFpEF”难题提供新的思路，为心脏康复治疗拓展新的研究方向。

Recent research confirms that aerobic rehabilitation exercise benefits heart failure with preserved ejection fraction (HFpEF), but its mechanism is unknown, which results in its limitation of clinical application. It has been known that cardiac macrophages (cMՓ) induced fibrosis is an essential pathological mechanism for the development of HFpEF. We found that aerobic exercise can reduce the number of cMՓ and its pro-inflammatory genes expression in HFpEF mice, which accompanied by increasing serum concentration of epoxyicosatetraenoic acids (EETs). We have evidenced that EETs is a critical mediator for aerobic exercise exerting its cardioprotective function. And EETs can inhibit the pro-inflammatory function of macrophages..Accordingly, we propose the hypothesis that aerobic exercise inhibits cMՓ by up-regulating EET levels, and then reduces cardiac fibrosis to protect HFpEF. In this project, we design to verify how aerobic exercise mediates cMՓ by EETs. Furthermore, we choose STAT6-HDAC3 axis as a core mechanism to demonstrate that EETs repress cMՓ via regulating histone deacetylation of its pro-inflammatory genes. This project aims to provide new ideas for the clinical problem of "how to effectively treat HFpEF", and also to expand new research directions for cardiac rehabilitation.