表皮干细胞外泌体通过调节巨噬细胞极化抑制慢性创面炎症的机制研究

皮肤的慢性创面因炎症期过长导致难愈。巨噬细胞（MΦ）是炎症反应的主要调节者，其表型转换（M1→M2）障碍是关键问题。MΦ极化与自噬密切相关，干细胞通过外泌体（exosome）对MΦ具有调节作用，为解决问题提供新思路。表皮干细胞（ESCs）是修复创面的理想种子细胞。前期研究证实:创面边缘注射ESCs-Exo，明显降低创面促炎因子TNF-α、IL-6的表达，加速创面愈合；缺氧刺激明显增强MΦ自噬水平。因此我们提出：在慢性创面中，ESCs通过外泌体调控MΦ自噬，影响其极化状态，减轻创面慢性炎症，促进创面愈合。本项目拟首先观察糖氧剥夺刺激下ESCs-Exo对MΦ自噬、极化等的影响，进一步在慢性创面观察ESCs-Exo对创面炎症水平、MΦ募集和极化等的调节作用，最后探讨自噬影响细胞极化的具体机制通路。本研究将为阐释自噬和极化的关系提供新证据，丰富皮肤创面免疫研究内容，为创面的非细胞治疗提供新思路。

Chronic wounds are difficult to heal due to prolonged inflammation. macrophages (MΦ) is the main regulator of inflammation, its phenotype transformation (M1 and M2) disorder is the key problem.MΦ polarization is closely related to the autophagy, stem cells have regulation effect on MΦpolarization through the exosome secretion, which provides new ideas to solve problems.Epidermal stem cells (ESCs) are ideal seed cells for wound healing.Previous studies confirmed that injection of Escs-Exo at the edge of wound significantly reduced the expression of TNF-α and IL-6, and accelerated wound healing.Hypoxia stimulation significantly enhance MΦ autophagy.Therefore, we proposed that in chronic wounds, epidermal stem cells regulate macrophage autophagy through exosomes, thereby affecting their polarization state, alleviating inflammation of chronic wound and promoting wound healing.In this project, at first to observe the effect of ESCs-exo on MΦautophagy, polarization and biological activity when stimulated by hypoxia; Further to observe the effect of ESCs-Exo on wound inflammation,MΦrecruitment and polarization in chronic wounds model; Finally to discuss specific pathways of MΦautophagy influence cell polarization.This study will provide new evidence to further explain the relationship between autophagy and macrophage polarization, enrich the research content of wound immune microenvironment, and provide new ideas for wound non-cellular therapy.