外泌体miR-155调控M1型巨噬细胞极化在狼疮性肾炎足细胞损伤中的作用及机制研究

足细胞炎性损伤是狼疮性肾炎（LN）发生发展的核心关键环节，但其作用机制尚不清楚。我们前期研究及相关研究发现， LN足细胞炎性损伤与外泌体miR-155、M1巨噬细胞极化相互间有密切关系。提示LN患者外泌体miR-155通过调控M1型巨噬细胞极化，促进LN足细胞炎性损伤和疾病的进展。本项目拟结合透射电镜、流式细胞术等技术，首先在细胞水平研究PBMCs外泌体miR-155调控M1型巨噬细胞极化在LN足细胞损伤中的作用机制；再在动物水平研究PBMCs外泌体miR-155表达、M1型巨噬细胞极化与LN的相关性并干预外泌体、miR-155对LN的作用机制；然后进一步通过临床验证PBMCs外泌体miR-155表达、M1型巨噬细胞极化与LN的相关性。本课题将从免疫微环境角度探讨LN新的细胞相互作用机制，为LN的发病进展提供新的理论依据，为该病的防治提供新的分子靶点，具有重要的研究价值和临床意义。

Podocyte inflammatory injury is the core and key link in the development of lupus nephritis (LN), but the mechanism remains unclear. Our previous studies have found that podocyte inflammatory injury is closely related to exosomes miR-155 and M1 macrophage polarization. The results suggest that exosomes miR-155 can promote podocyte inflammatory injury and the progression of the disease by regulating the polarization of M1 macrophages in LN. In this project, first of all, transmission electron microscopy and flow cytometry are used to study the mechanism of exosomes miR-155 in regulating M1 macrophage polarization during podocyte injury of LN at the cellular level. And then, we will study the correlation between peripheral blood mononuclear cells (PBMCs) exosomes miR-155 expression, M1 macrophage polarization and LN at the animal level, and intervene exosomes miR-155 expression to study its role in LN. Furthermore, the relationship between the PBMC exosomes miR-155 expression, M1 macrophage polarization and LN were confirmed by clinical experiments. This project will explore the mechanism of cell interaction in LN from a new perspective of immune microenvironment, then provide a new theoretical basis for the pathogenesis of LN, and a new molecular target for the prevention and treatment of LN, which has important research value and clinical significance.