基于HIF-1α/mTOR介导的细胞自噬探讨苗药金乌健骨胶囊对类风湿关节炎的骨保护机制

类风湿关节炎（RA）的发病机制尚不清楚，据最新国内外文献分析，低氧诱导因子1α（HIF-1α）和雷帕霉素靶蛋白（mTOR）在RA滑膜炎症、细胞增殖、血管生成及骨破坏中发挥重要作用。通过调控HIF-1α/mTOR信号介导的细胞自噬相关基因以及下游趋化因子、炎性细胞因子及破骨细胞标志物等的异常表达可能是逆转RA骨破坏的重要途径。因此，课题组在前期研究基础上，提出以苗医“痹毒”结合中医“肾虚邪郁”理论指导下组成的苗药金乌健骨胶囊可能通过调控HIF-1α/mTOR信号轴介导的破骨细胞自噬，抑制破骨细胞异常增殖及活化，从而阻断RA骨破坏的科学假说，据有充分的理论依据和坚实的研究基础。为验证该假说，我们拟通过建立RA动物模型及人破骨细胞模型，探讨苗药金乌健骨胶囊对HIF-1α/mTOR信号介导的自噬及相关基因的调控作用，从新的角度探讨该药对RA骨破坏的保护机制，有望为RA的治疗发掘新的民族药。

The pathogenesis of rheumatoid arthritis (RA) is unclear. According to the latest domestic and foreign literature analysis，hypoxia-inducible factor 1α (HIF-1α) and rapamycin target protein (mTOR) play an important role in synovial inflammation, cell proliferation, angiogenesis and bone destruction in RA patients. Regulating the abnormal expression of autophagy-related genes, downstream chemokines, inflammatory cytokines and osteoclast proliferation activation markers mediated by HIF-1α/mTOR signal may be an important way to reverse RA bone destruction. Therefore, on the basis of previous research, the group proposed a scientific hypothesis that MiaoYao Jinwujiangu capsules which based on the theory of Miao medicine — “Bi du”combined with Chinese medicine —“Shen xu xie yu” , may inhibit the abnormal proliferation and activation of osteoclasts by regulating osteoclast autophagy mediated by the HIF-1α / mTOR signal axis, and prevent bone destruction. The hypothesis has a sufficient theoretical basis and a solid research foundation. To verify this hypothesis, we intend to explore the regulatory effect of Miao Yao Jinwujiangu capsules on HIF-1α / mTOR signal-mediated autophagy and related genes by establishing RA animal models and human osteoclast models. This research focused on the potential mechanism to protect the bones of RA from a new perspective, and it is expected to explore new national medicine for RA treatment.