椎间盘退变（IDD）是脊柱退行性病变的重要病理基础，严重影响人民健康和生活质量。巨噬细胞M1型极化广泛存在于IDD中并在其进展中发挥重要作用。研究表明，外泌体可通过转运miRNA调控巨噬细胞极化，然而其在IDD中对巨噬细胞极化的作用仍不明确。我们前期发现退变髓核细胞外泌体miR-27a可进入巨噬细胞并促进其M1型极化，靶基因预测PPARγ及下游通路可能是该机制的重要原因。因此，本课题拟针对IDD中巨噬细胞M1型极化机制展开以下研究：1.明确IDD患者髓核细胞外泌体miR-27a表达、巨噬细胞M1型极化及退变等级相关性；2.阐明髓核细胞外泌体miR-27a与靶基因PPARγ及下游通路对巨噬细胞M1型极化的调控机制；3.探索外泌体miR-27a调控在IDD模型中对巨噬细胞极化的影响及其治疗作用。本课题将首次阐明髓核细胞外泌体在IDD中巨噬细胞M1型极化中的关键作用，为IDD相关治疗奠定基础。

Intervertebral disc degeneration (IDD) has long been regarded as a pathological basis of degenerative spinal diseases, which severely impact public health and life quality. Macrophage M1 polarization is widely observed in IDD and plays an important role in IDD progress. Accumulating evidence has shown that exosomes could regulate macrophage polarization as miRNA carriers. However, there is no study regarding the role of exosomes in macrophage polarization in IDD. Previously, we found that degenerated nucleus pulposus cell-derived exosomes (NP-exos) could induce macrophage M1 polarization by delivering miR-27a. PPARγ was considered as the target gene of miR-27a by microRNA target prediction in this effect. Accordingly, to reveal the underlying mechanism of macrophage M1 polarization in IDD, the following studies are scheduled: (1) statistical analysis of NP-exos derived miR-27a level, macrophage M1 polarization and IDD degree in IDD patients. (2) clarification of the role of NP-exo derived miR-27a and its target gene PPARγ in macrophage M1 polarization. (3) exploration of NP-exos derived miR-27a regulation in macrophage M1 polarization and its curative effect in IDD model. This project will clarify the essential role of NP-exos in macrophage M1 polarization of IDD, thus provide important theoretical basis for IDD treatment.