基于Wnt-Notch信号探讨苗药五藤膏治疗膝骨关节炎的分子机制

膝骨关节炎（KOA）的发病机制尚不完全清楚。据最新的国内外研究证实，Wnt和Notch信号在KOA软骨细胞分化、增殖和凋亡、维持软骨细胞表型及基质代谢等方面发挥重要角色，其信号通路的异常激活可能是软骨细胞代谢失衡和KOA形成的关键因素。本课题根据苗医学“壅塞为病，通达为康”的外治理论，提出“通筋散血”的治疗方法，以贵州苗药为主组成五藤膏，以Notch-Wnt信号为靶向研究五藤膏对KOA模型软骨细胞Wnt上下游基因和Notch受体与相应配子的表达水平，探讨苗药五藤膏调节KOA软骨细胞Wnt-Notch信号相关基因的分子机制。为此，我们在前期研究的基础上，提出Wnt和Notch信号为KOA软骨细胞病变的关键调节因子，苗药五藤膏可能通过调控KOA软骨细胞Wnt和Notch信号相关基因和蛋白的表达水平，从而维持KOA软骨细胞分化、增殖与凋亡平衡的科学假说，具有坚实的理论依据和充分的研究基础。

The pathogenesis of knee osteoarthritis(KOA) is not entirely clear. The latest domestic and foreign study have confirmed that Wnt and Notch signal play an important role in KOA chondrocyte differentiation, proliferation and apoptosis, and also have important significance in the maintenance of chondrocyte phenotype and substrate metabolism,the abnormal activation of signal pathway may be the key factor lead to the imbalance of chondrocyte metabolism and the formation of KOA. This topic based on the Miao medicine theory of external therapy“choking for disease,dredging for health”,put forward the therapy of “dredging sinew and scattering blood”,have composed the Wuteng Plaster which mainly includes local Miao medicine,targeted for Notch-Wnt signal to research the effect of Wuteng plaster for the expression level of Wnt signal upstream and downstream gene,Notch receptors and corresponding gametes in KOA model chondrocyte,to discuss the molecular mechanism of Miao medicine Wuteng plaster in regulating the related genes of Wnt-Notch signal in KOA chondrocyte.for this, We based on the previous studies,propose the scientific hypothesis that Wnt and Notch signal may be the key regulatory factors in the KOA chondrocyte lesion,Miao medicine Wuteng plaster maybe maintain the balance of chondrocyte differentiation, proliferation and apoptosis by regulating and controlling the expression level of related genes and protein in Wnt and Notch signal in KOA chondrocyte,this hypothesis has solid theoretical basis and sufficient research foundation.