我们前期研究发现在心肌梗死后有大量的巨噬细胞浸润并参与梗死损伤修复过程。在对巨噬细胞SENP1缺失的小鼠骨髓巨噬细胞进行分析时，证实SENP1的缺失导致巨噬细胞表现为M2样的功能。因此，我们提出SENP1调控巨噬细胞的活化参与了心肌梗死的修复过程，并对之后心脏的重构与功能恢复产生影响。在本课题中，我们将重点研究如下科学问题：1. 巨噬细胞中SENP1的表达对心肌梗死修复有什么样作用？2. 在心肌梗死修复过程中SENP1如何调控巨噬细胞的活化？3. SENP1如何通过巨噬细胞调控心肌梗死修复的病理过程？我们将通过建立SENP1巨噬细胞特异性敲除小鼠的心肌梗死模型来解析这些问题。对这些问题的回答将使我们在了解SENP1调控巨噬细胞活性基础上，进一步认识与理解SENP1在心肌梗死修复中的作用和意义，以及SENP1作为治疗靶标在心血管临床中应用的可能性与策略。

In preliminary studies, we found abound macrophages infiltration in myocardial infarcted field, which affects the repair and function recovering process after infarction. We also found the macrophages with SENP1 deficiency were activated as M2 type polarization. We hypothesize that SENP1 regulates macrophage activation in the infarcted field, which might play an important role in myocardial repair process. In this proposal, we will test this hypothesis in the following specific aims: 1. To determine whether SENP1 in macrophages play a role in the repair of myocardial infarction. 2. To determine how does SENP1 regulate macrophage activation during myocardial infarction. 3. To determine how does SENP1 in macrophages affect the repair process of myocardial infarction. Successfully completion of this proposal will yield new information about the role of SENP1 in macrophage activation and in the repair process of myocardial infarction.