“温通法”火针调控间充质干细胞归巢介导巨噬细胞极化干预膝骨关节炎的机制研究

膝骨关节炎（KOA）是一种低度炎症状态，巨噬细胞向M2极化失败是其关键病理机制。研究显示：趋化因子SDF-1能引起间充质干细胞（MSCs）归巢，MSCs可调控巨噬细胞向M2极化（M1/M2极化平衡），抑制炎性免疫微环境。申请人临床研究发现：火针能显著缓解KOA患者疼痛，提高SDF-1分泌；基础实验发现：火针能降低M1分泌的IL-1α、TNF-α等促炎因子，提高M2分泌的IL-10、TGF-β等抗炎因子，发挥软骨修复作用。据此本课题以“火针通过趋化因子SDF-1/CXCR4轴，调控MSCs归巢，使巨噬细胞向M2极化，发挥抗炎软骨修复作用”为假说，选用内侧半月板不稳KOA小鼠，采用自主研发的能控制温度和深度的智能电子火针，以SDF-1/CXCR4轴为起始靶点，以MSCs调控巨噬细胞极化为核心，应用分子探针介导的Micro-PET、慢病毒转染、悬液芯片等技术，阐明“温通法”火针干预KOA的机制。

Knee osteoarthritis (KOA) is a low-grade inflammatory state, and the failure of macrophage M2 polarization is the key pathological mechanism. Studies have shown that the chemokine SDF-1 can cause homing of mesenchymal stem cells (MSCs). MSCs can regulate the M2 polarization of macrophages (M1 / M2 polarization balance) and inhibit the inflammatory immune microenvironment. The applicant's research found that: clinical fire needle can significantly relieve pain and increase SDF-1 secretion in patients with KOA. In basic experiments, fire needle can reduce pro-inflammatory factors such as IL-1α and TNF-α secreted by M1, increase anti-inflammatory factors such as IL-10 and TGF-β secreted by M2, and play a role in cartilage repair. Therefore, the project is based on the hypothesis that fire needle regulate the homeostasis via SDF-1/CXCR4 axis polarize macrophages to M2, and promote cartilage generation via anti-inflammation. KOA mice are selected and intelligent electronic fire needle are used to precisely control temperature and depth. Use SDF-1/CXCR4 axis as the initial target, set the regulation of MSCs to polarize macrophages as the core, apply molecular probes to mediate Micro-PET, and adopt slow virus transfection, suspension chip and other techniques in order to demonstrate the mechanism of fire needle on KOA based on 〝Wentong〞 theory.