BM-MSC-exosomes LncRNA XR_001836271.1调控miR-132-3p影响巨噬细胞极化改善心力衰竭的机制研究

心力衰竭是心血管病的终末阶段且预后差，巨噬细胞极化是其重要的病理生理机制。目前间充质干细胞外泌体在治疗心衰中的作用引起广泛关注，但机制尚不明确。申请人已证实骨髓源间充质干细胞外泌体BM-MSC-exosomes可促进巨噬细胞极化且有效改善心衰小鼠心功能，其携带的XR_001836271.1与心衰相关的miRNA-132-3p相互作用。故申请者提出假说BM-MSC-exosomes LncRNA XR_001836271.1通过竞争性结合miR-132-3p促进巨噬细胞向抗炎表型转换，以改善心衰。本课题拟用富集XR_001836271.1的BM-MSC-exosomes治疗心衰小鼠，检测心功能、巨噬细胞极化和炎症因子的表达；并进一步在体外探究LncRNA XR_001836271.1/miR-132-3p/FOXO通路在诱导巨噬细胞极化中的作用。此研究将为心衰治疗提供新的理论基础和治疗靶点。

Heart failure is the terminal stage of cardiovascular disease with a poor prognosis, and macrophage polarization is an important pathophysiological mechanism involved in this process. At present, the role of mesenchymal stem cell exosomes in the treatment of heart failure has raised widespread attention, but the mechanism is still unclear. The applicant has demonstrated that the bone marrow-derived mesenchymal stem cell exosomes promote the polarization of macrophages and effectively enhance cardiac function of mice with heart failure. The interaction between XR_001836271.1 and heart failure associated miRNA-132-3p was carried out. Hence, the applicant proposes the hypothesis that BM-MSC-exosomes LncRNA XR_001836271.1 promotes the conversion of macrophages to an anti-inflammatory M2 phenotype by competitively binding miR-132-3p, therefore, repair cardiac function. This project aims to use LncRNA XR_001836271.1 enriched BM-MSC-exosomes to treat heart failure mice, by evaluating the effect of the cardiac function, macrophage polarization and the expression of inflammatory cytokines. Further, we intend to in vitro explore the mechanism of LncRNA XR_001836271.1/miR-132-3p/FOXO signaling pathway in inducing macrophage polarization. This research provides a new theoretical basis and therapeutic target for the treatment of heart failure.