单体原苏木素A通过去乙酰化修饰调控心脏CD4+T细胞代谢及功能表型进而改善心梗后心脏重构的机制

心肌梗死（MI）后心衰发病率高且预后差，临床防治成为瓶颈难题。MI后心脏重构（CR）是其重要病理机制，而免疫炎症是主要促发因素，其中T细胞作用关键。既往课题组率先提出心脏T细胞代谢重塑是介导其功能紊乱并促进CR的重要因素。因此调控T细胞免疫代谢或成为MI后CR防治的新策略。课题组拥有中药单体原苏木素A（PrA）免疫调节作用的知识产权，预实验首次证实PrA改善MI后CR，利用10X单细胞测序绘制出心脏免疫细胞图谱，识别PrA作用的免疫亚群CD4+T细胞的免疫/代谢表征和潜在靶点。因此提出：PrA通过HDAC1去乙酰化重塑心脏CD4+T细胞代谢介导其向免疫调节功能及表型转换，维持心脏免疫微环境稳态改善MI后CR。本课题明确PrA在MI后CR中的创新应用并筛选衍生物；聚焦免疫代谢的新视角，揭示PrA通过“表观-代谢-免疫”交互调控的心脏保护机制；为临床防治提供新思路，推动单体药物研发和临床转化。

Heart failure after myocardial infarction (MI) has high incidence and poor prognosis. While the targeted clinical prevention and treatment have become bottleneck problems. Immune inflammation triggered cardiac remodeling (CR) is its important pathological mechanism, in which T cells play a key role. Previously, our research team firstly proposed that cardiac T cell metabolic remodeling is an important factor to mediate its dysfunction and further promotes CR. Therefore, regulating T cell immune metabolism may become a novel strategy for CR prevention and treatment after MI. Our research team owns the intellectual property rights of the monomeric Protosappanin A (PrA) immunomodulatory effect. The pre-experiment confirmed for the first time that PrA improves CR after MI. Using 10X single-cell sequencing to draw a map of cardiac immune cells, we identified PrA immune-metabolic characterization and potential targets for the key immune subsets CD4+T cells. Thus, it is proposed that PrA remodels cardiac CD4+T cell metabolism to convert to immune regulation and phenotype via targeting HDAC1 mediated deacetylation effect, and further improves CR after MI by maintaining the cardiac immune microenvironment homeostasis. This project proposes the innovative application of PrA in CR after MI and screens for derivatives. Moreover, we focus on a newly perspective on immune metabolism, revealing the protective mechanism of PrA through the "epigenetics-metabolic-immunity" interactive regulation. Our research will provide novel ideas for clinical prevention and treatment of CR after MI, promoting Monomeric drug development and clinical transformation.