TLR4/NF-κB信号通路在激素性股骨头坏死的作用  

Role of TLR4/NF-κB signaling pathway in steroid-induced osteonecrosis of the femoral head

作　　者：徐玉娟 马良辰 田富宝 朱宁[2] XU Yu-juan;MA Liangchen;TIAN Fu-bao;ZHU Ning(Ningxia Medical University,Yinchuan750004,China;Department of Rehabilitation Medicine,General Hospital,Ningxia Medical University,Yinchuan 750004,China;Ningdong Hospital,Ningxia Hui Autonomous Region,Yinchuan,750400,China)

机构地区：[1]宁夏医科大学,宁夏银川750004 [2]宁夏医科大学总医院康复医学科,宁夏银川750004 [3]宁夏回族自治区宁东医院,宁夏银川750400

出　　处：《中国矫形外科杂志》2024年第10期895-900,共6页Orthopedic Journal of China

基　　金：国家自然科学基金资助项目(编号:81760904);宁夏医科大学总医院“国家自然科学基金项目孵育计划”。

摘　　要：激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)是由于糖皮质激素的大量使用最终造成股骨头坏死的一种代谢性疾病,而SONFH的发病机制迄今仍未完全明确,存在各种假说。研究表明,巨噬细胞参与的炎症反应可能是激素性股骨头坏死发生发展的重要促发因素之一。Toll样受体4(toll like receptor 4,TLR4)/核转录因子-κB(nuclear factor kappa-B,NF-κB)炎症信号通路能被短期内过量或长期使用的糖皮质激素激活,致NF-κB活化,使其原有结构发生改变,继而转入细胞核启动基因表达释放出大量炎性介质,如肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、白细胞介素-1β(interleukin-1beta,IL-1β)、白细胞介素-6(interleukin-6,IL-6)等,使破骨细胞分化增强,骨吸收增加,同时抑制成骨细胞分化和骨形成,诱发其凋亡,对骨的结构造成影响,破坏骨稳态,最终引发股骨头塌陷、坏死。本文对TLR4/NF-κB信号通路参与SONFH进展的可能作用机制进行综述,为SONFH的预防和治疗提供新思路。Steroid-induced osteonecrosis of the femoral head(SONFH)is a metabolic disease caused by the extensive use of glucocorti⁃coid.The pathogenesis of SONFH is still not completely clear,yet there are various hypotheses.Studies have shown that the inflammatory re⁃action of macrophages may be one of the important factors to impel the development of SONFH.The TLR4/NF-κB inflammatory signaling pathway can be activated by excessive glucocorticoid in the short-term or long term,resulting in the activation of NF-κB,which changes the original structural state of NF-κB,and then transmits to the nuclear promoter gene expression to release a large number of inflammatory me⁃diators,such as TNF-α,Il-1β,IL-6,etc.They inhibits osteoblast differentiation and bone formation,induces osteoblast apoptosis,at the same time,enhances osteoclast differentiation,increases bone resorption and destroys bone homeostasis,eventually leading to collapse and necrosis of femoral head.This article reviews the possible mechanism of TLR4/NF-ΚB signaling pathway in the progression of SONFH,pro⁃viding a reference for the prevention and treatment of SONFH.

关 键 词：TLR4受体 股骨头坏死 糖皮质激素 综述 

分 类 号：R318[医药卫生—生物医学工程]