lncRNA GAS5海绵吸附miR-34a靶向调控p53/Bcl-2软骨细胞凋亡途径参与针刀疗法延缓膝骨性关节炎软骨退变的机制研究

针刀作为一种非药物疗法，可调节膝关节异常机械应力、提高膝骨关节炎（KOA）患者运动功能，已被多个临床指南推荐。我们前期研究发现，针刀疗法可减少软骨细胞凋亡，延缓膝关节软骨退变，但机制不明。研究表明，在异常机械应力介导的KOA进展过程中，非编码RNA的调控发挥了重要作用：抑制lncRNA GAS5，可以通过海绵吸附效应下调microRNA-34a，从而抑制p53/Bcl-2凋亡途径，减少膝关节软骨细胞凋亡。本课题以改良Videman法制备KOA兔模型，结合行为学、影像学及分子生物学技术，探讨lncRNA GAS5/miR-34a软骨细胞凋亡途径在针刀疗法改善KOA兔膝关节运动功能、关节面机械应力环境及软骨退变中的关键作用；再进一步构建lncRNA GAS5过表达慢病毒载体，阐明针刀作用于该凋亡途径的分子机制。本研究将有助于深入了解针刀治疗KOA的机制，并为其在KOA康复中的应用提供科学依据。

Acupotomology, as a nonpharmacological therapy, has been recommended by several clinical guidelines for regulating abnormal mechanical stress in the knee and improving motor function in patients with knee osteoarthritis (KOA). Our previous studies have found that acupotomology therapy can reduce chondrocyte apoptosis and delay knee cartilage degeneration, but the underlying mechanism is unclear. Studies have shown that the regulation of non-coding RNA plays an important role in the abnormal mechanical stress-mediated progression of KOA: Inhibiting lncRNA GAS5 can down-regulate microRNA-34a via the sponge adsorption effect, then the p53/Bcl-2 apoptotic pathway was inhibited to reduce the apoptosis of knee chondrocytes. In this study, the modified Videman method was used to prepare KOA rabbit model. Combined with behavioral, imaging and molecular biology techniques, the key role of lncRNA GAS5/miR-34a chondrocyte apoptosis pathway in the regulation of knee joint motor function, articular surface mechanical stress environment and cartilage degeneration by acumotometry was explored. LncRNA GAS5 overexpressed lentiviral vector was further constructed to clarify the molecular mechanism of acupotomology acting on the apoptotic pathway. This study will help to further understand the mechanism of acupotomology in the treatment of KOA and provide a scientific basis for its application in the rehabilitation of KOA.