基于OPG/RANK/RANKL信号通路防治股骨头坏死的中医药研究进展

Traditional Chinese Medicine in Prevention and Treatment of Osteonecrosis of Femoral Head Based on OPG/RANK/RANKL Signaling Pathway:A Review

股骨头坏死(ONFH)是由于股骨头内的供血发生损害,细胞组织等发生变性,逐渐造成骨结构被破坏,股骨头进行性塌陷引起的疼痛及功能障碍性疾病。ONFH的主要病理机制在于微循环损害细胞组织能力下降、骨的吸收与新生骨的重建之间的平衡被破坏,其生物力学发生改变,加速股骨头坏死的病理进展。早期临床表现并不明显,主要为髋部或腹股沟区疼痛或酸痛,休息后可缓解,疾病发展后期可出现疼痛加剧,肢体短缩,下肢无力,行走困难或跛行。目前临床上西医常用促骨形成药、抗凝药和人工关节置换等治疗,但也存在假体松动、感染等诸多问题。研究表明,中医药治疗ONFH从整体出发,应用多功能、多靶点、多系统的中药治疗,保障了治疗途径的安全性和有效性。骨保护素(OPG)/核转录因子-κB受体活化因子(RANK)/核转录因子-κB受体活化因子配基(RANKL)信号通路在维持骨重建的动态平衡中具有关键地位,该通路利用中医药等治疗方式促进生物体内破骨细胞凋亡,减少骨吸收,加速骨形成,对于防治ONFH具有重要作用。该文通过查阅国内外相关文献,对OPG/RANK/RANKL信号通路影响相关细胞因子表达在ONFH中的作用,中药单体、中药复方及中药复方联合物理治疗增加成骨细胞分泌,促进OPG表达,提高细胞因子等表达水平,抑制破骨细胞活性等方式以防治ONFH的研究现状进行综述,为中医药防治ONFH提供新的思路和方向。

Osteonecrosis of the femoral head(ONFH)is a painful and debilitating disease caused by impaired blood supply to the femoral head and cellular and tissue degeneration,leading to gradual destruction of the bone structure and progressive collapse of the femoral head.The main pathological mechanism of ONFH is the disruption of the balance between bone absorption and the reconstruction of new bone,resulting from microcirculation damage and decreased cellular tissue ability.This imbalance leads to biomechanical changes and accelerates the pathological progression of ONFH.In the early stages,clinical manifestations may not be obvious,mainly presenting as pain or discomfort in the hip or groin area,which can be relieved after rest.In the later stage of the disease,pain intensifies,and limb shortening,lower limb weakness,difficulty walking,or limping may occur.Currently,western medicine commonly uses osteogenic agents,anticoagulants,and artificial joint replacement for treatment,but there are also many issues such as prosthesis loosening and infection.Research has shown that traditional Chinese medicine(TCM)treatment of ONFH takes a holistic approach and employs multi-functional,multi-target,and multi-system Chinese medicine therapies,ensuring the safety and effectiveness of the treatment.The osteoprotegerin(OPG)/receptor activator of nuclear factor-κB(RANK)/RANK ligand(RANKL)signaling pathway plays a crucial role in maintaining the dynamic balance of bone remodeling.TCM treatments utilize this pathway to promote apoptosis of osteoclasts,reduce bone resorption,and accelerate bone formation,thereby playing an important role in the prevention and treatment of ONFH.This paper reviewed the role of OPG/RANK/RANKL signaling pathway and related cytokine expression in ONFH by reviewing relevant literature in China and abroad and research status of Chinese medicinal monomers,Chinese medicinal formulations,and combinations with physical therapy in increasing osteoblast secretion,promoting OPG expression,enhancing cytokine expression levels,and inhibiting osteoclast activity for the prevention and treatment of ONFH.This paper is expected to provide new ideas and directions for TCM in the prevention and treatment of ONFH.