低强度脉冲超声作用于膝骨关节炎炎症相关信号通路的研究进展  

Progress in Study of Low-Intensity Pulsed Ultrasound Acting on Inflammation-Related Signaling Pathways in Knee Osteoarthritis

作　　者：欧阳辉[1,2] 林星瑾[1,2] 王金英 沈龙彬 王成栋 OUYANG Hui;LIN Xingjin;WANG Jinying;SHEN Longbin;WANG Chengdong(The First Affiliated Hospital of Jinan University,Guangzhou,Guangdong 510630,China;Jinan University,Guangzhou,Guangdong 510620,China)

机构地区：[1]暨南大学附属第一医院,广东广州510630 [2]暨南大学,广东广州510620

出　　处：《康复学报》2023年第5期470-476,共7页Rehabilitation Medicine

基　　金：国家重点研发计划项目(2020YEC2005700);广州市基础研究计划市校(院)联合资助项目(202201020082)。

摘　　要：膝骨关节炎(KOA)是一种包含关节软骨、滑膜、软骨下骨以及关节周围韧带肌肉等组织结构发生病理性改变的退行性全关节疾病。KOA的发病与关节软骨的代谢失衡及细胞因子的启动有关,特别是白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的高表达。其出现于KOA的多条致病信号通路中,调控KOA的细胞内活动,在软骨细胞破坏、细胞外基质减少、软骨重塑异常、软骨下骨化和滑膜炎症等病理过程中扮演重要的角色。低强度脉冲超声(LIPUS)作为一种无创安全的物理治疗手段,其本质上是一种强度较低的机械能,通过其空化效应等物理刺激可以使其效应细胞产生一系列理化反应。LIPUS在KOA的临床应用中疗效确切,可通过调节IL-1β和TNF-α等炎症相关信号通路的活性而达到消炎止痛、促进软骨修复的作用。其治疗机制包括:①LIPUS可通过增强滑膜中巨噬细胞的自噬途径及抑制核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体通路使巨噬细胞产生IL-1β减少,减轻炎症反应;也可通过经典无翅型MMTV整合位点家族蛋白(Wnt)/β-连环蛋白信号通路作用于滑膜中的成纤维细胞从而抑制滑膜纤维化。②LIPUS通过抑制IL-1β诱导的核因子活化B细胞κ轻链增强子(NF-κB)信号通路及调控丝裂原活化蛋白激酶(MAPKs)信号通路来促进软骨细胞生成细胞外基质,调节软骨细胞代谢,保护软骨。③LIPUS通过激活细胞外信号调节激酶1/2(ERK1/2)和磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)信号通路促进间充质干细胞增殖分化,也可通过整合素-雷帕霉素靶蛋白(mTOR)信号通路来促进间充质干细胞产生转化生长因子β1(TGF-β1)以促进软骨形成。最新研究还发现LIPUS通过自噬途径促进间充质干细胞的迁移和外泌体释放来修复软骨,为未来LIPUS的联合治疗方向提供新思路。通过对LIPUS作用于KOA炎症相关信号通路的研究进展�Knee osteoarthritis(KOA)is a degenerative total joint disease involving pathological changes in the cartilage,synovium,subchondral bone,and periarticular ligaments and muscles of the joint.The onset of KOA is associate with the metabolic imbalance of articular cartilage and the activation of cytokines,especially the high expression of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α).They appear in multiple pathogenic signaling pathways of KOA,regulate the intracellular activity of KOA and play an important role in pathological processes such as chondrocyte destruction,extracellular matrix reduction,abnormal cartilage remodeling,subchondral ossification,and synovial inflammation.Low-intensity pulsed ultrasound(LIPUS),as a non-invasive and safe physiotherapy therapy,is essentially a low intensity mechanical energy,which can produce a series of physicochemical effects on cells through physical stimulation such as cavitation effect.LIPUS is effective in the treating KOA,achieving anti-inflammatory and analgesic effects and promoting cartilage repair by modulating the activity of inflammation-related signaling pathways such as IL-1βand TNF-α.The therapeutic mechanisms reviewed as following:1)LIPUS can reduce the inflammatory response by enhancing the autophagic pathway of macrophages in the synovial membrane and inhibiting the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammatory vesicle pathway to reduce IL-1βproduction by macrophages;it can also acts through the classical wingless MMTV integration site family protein(Wnt)/β-linked protein signaling pathway on fibroblasts in the synovial membrane to inhibit synovial fibrosis.2)LIPUS promotes chondrocyte production of extracellular matrix,regulates chondrocyte metabolism,and protects cartilage by inhibiting IL-1β-induced nuclear factor-activated B-cellκlight chain enhancer(NF-κB)signaling pathway and regulating mitogen-activated protein kinases(MAPKs)signaling pathway.3)LIPUS protects cartilage by activating extracellul

关 键 词：膝骨关节炎 低强度脉冲超声 炎症 信号通路 滑膜细胞 软骨细胞 间充质干细胞 

分 类 号：R684.3[医药卫生—骨科学]