脂氧素A4介导滑膜巨噬细胞M2极化调控软骨细胞焦亡在运动治疗骨关节炎中的作用及机制研究

前期研究发现，脂氧素A4（LXA4）具有快速生成及分解的特点，在骨关节炎（OA）运动疗法中发挥重要保护作用。LXA4不仅降低全身及局部的慢性炎症，还抑制外周神经敏感性从而缓解疼痛。据此特点，测定体内LXA4含量变化有望成为一种监测合理运动的指标。结合生物信息学分析及预实验验证，本课题重点聚焦于LXA4介导滑膜巨噬细胞M2极化调控软骨细胞焦亡途径，进一步剖析LXA4在OA运动疗法中的作用机制。本研究将在在体OA模型上，研究跑台运动与LXA4生成及软骨损伤的关系，明确LXA4介导滑膜巨噬细胞M2极化在OA运动疗法中发挥的作用。同时应用Transwell小室技术，将滑膜巨噬细胞和软骨细胞共培养。通过Flexcell细胞应力加载系统，观察LXA4及力学刺激调控滑膜巨噬细胞M2极化对软骨细胞焦亡的影响，明确此信号通路在运动治疗OA中的作用，阐明OA运动疗法的分子机制，为OA运动疗法提供理论基础。

Previous studies have found that lipoxin A4 (LXA4) has the characteristics of rapid synthesis and decomposition, which plays an important protective role in exercise therapy for osteoarthritis (OA). LXA4 can not only reduce systemic and local chronic inflammation, but also inhibit peripheral nerve sensitivity to relieve pain. According to this feature, LXA4 is expected to be an effective index to monitor the exercise for curing OA. Combined with bioinformatics analysis and pre-experimental verification, the research focuses on LXA4 mediated M2 polarization of synovial macrophages regulating chondrocyte pyrosis pathway, and further analyzes the mechanism of LXA4 in exercise therapy of OA. In the beginning, we will study the relationship among treadmill training and LXA4 synthesis and cartilage injury on OA model in vivo, and clarify the role of LXA4 mediated M2 polarization of synovial macrophages in exercise therapy of OA. Furthermore, synovial macrophages and chondrocytes are co-cultured through Transwell chamber technology. Using Flexcell system, the effect of LXA4 and mechanical stimulation on chondrocyte pyroptosis by regulating M2 polarization of synovial macrophages are investigated. Moreover, the signal pathway in the process of OA exercise therapy is clarified, and the molecular mechanism of OA exercise therapy is elucidated, and a theoretical basis for OA exercise therapy is provided.