NF-κB通路调控IL-6/hs-CRP/TNF-α表达与 踝关节骨折临床表现及预后的 关联性研究进展
Research Progress on the Association between NF-κB Pathway Regulation of IL-6/hs-CRP/TNF-α Expression and Clinical Manifestations as Well as Prognosis in Ankle Fractures
DOI: 10.12677/acm.2026.1631075, PDF,    科研立项经费支持
作者: 付海燕：云南中医医药大学第四附属医院，云南 昆明；冯新越, 许争光*：云南省玉溪市中医医院，云南 玉溪
关键词: NF-κB；IL-6/hs-CRP/TNF-α；炎症联级；踝关节骨折；预后；NF-κB； IL-6/hs-CRP/TNF-α； Inflammatory Cascade； Ankle Fracture； Prognosis
摘要: 在踝关节发生骨折时，可诱导发生炎症反应，NF-κB信号通路作为炎症反应的重要通路来调控IL-6/hs-CRP/TNF-α表达引起骨折的一系列核心临床表现，就这些核心的临床表现来对骨折患者预后做出预测，文章将从机制、临床表现、预后评估等多个维度，系统阐述这一调控网络在踝关节骨折中的临床价值，为精准医疗在骨科创伤领域的应用提供理论依据。
Abstract: When an ankle fracture occurs, it can induce an inflammatory response. The NF-κB signaling pathway, as a crucial pathway in inflammation, regulates the expression of IL-6, hs-CRP, and TNF-α, leading to a series of core clinical manifestations in fractures. Based on these core clinical features, predictions can be made regarding patient prognosis. This article systematically elaborates on the clinical value of this regulatory network in ankle fractures from multiple dimensions, including mechanisms, clinical manifestations, and prognostic assessment, providing a theoretical basis for the application of precision medicine in orthopedic trauma.
文章引用：付海燕, 冯新越, 许争光. NF-κB通路调控IL-6/hs-CRP/TNF-α表达与 踝关节骨折临床表现及预后的 关联性研究进展[J]. 临床医学进展, 2026, 16(3): 2744-2752. https://doi.org/10.12677/acm.2026.1631075

参考文献

[1] 刘松. 踝关节骨折流行病学及成人踝关节骨折手术部位感染危险因素研究[D]: [博士学位论文]. 石家庄: 河北医科大学, 2019.
[2] 姚立东. 踝关节骨折的诊断和治疗[J]. 家庭科技, 2021(8): 51-52.
[3] 李石伦, 李傲, 崔鹏, 等. 中国西部与东部地区2010至2011年成人Barton骨折的流行病学特点[J]. 中华医学杂志, 2019, 99(1): 62-66.
[4] 胥少, 葛宝丰, 徐印坎. 实用骨科学[M]. 第4版. 北京: 人民军医出版社, 2015: 1060-1067.
[5] Zinatizadeh, M.R., Schock, B., Chalbatani, G.M., Zarandi, P.K., Jalali, S.A. and Miri, S.R. (2021) The Nuclear Factor Kappa B (NF-κB) Signaling in Cancer Development and Immune Diseases. Genes & Diseases, 8, 287-297. [Google Scholar] [CrossRef] [PubMed]
[6] Barnabei, L., Laplantine, E., Mbongo, W., Rieux-Laucat, F. and Weil, R. (2021) NF-κB: At the Borders of Autoimmunity and Inflammation. Frontiers in Immunology, 12, Article 716469. [Google Scholar] [CrossRef] [PubMed]
[7] Alharbi, K.S., Fuloria, N.K., Fuloria, S., Rahman, S.B., Al-Malki, W.H., Javed Shaikh, M.A., et al. (2021) Nuclear Factor-κB and Its Role in Inflammatory Lung Disease. Chemico-Biological Interactions, 345, Article ID: 109568. [Google Scholar] [CrossRef] [PubMed]
[8] 秦航, 范士洁, 罗智成, 等. TLR/NF-κB信号轴预测开放性骨折患者骨感染的价值[J]. 实用临床医药杂志, 2024, 28(21): 82-88.
[9] Sen, R. and Baltimore, D. (1986) Inducibility of Κ Immunoglobulin Enhancer-Binding Protein NF-κB by a Posttranslational Mechanism. Cell, 47, 921-928. [Google Scholar] [CrossRef] [PubMed]
[10] Manou-Stathopoulou, S. and Lewis, M.J. (2021) Diversity of NF-κB Signalling and Inflammatory Heterogeneity in Rheumatic Autoimmune Disease. Seminars in Immunology, 58, Article ID: 101649. [Google Scholar] [CrossRef] [PubMed]
[11] Yu, H., Lin, L., Zhang, Z., Zhang, H. and Hu, H. (2020) Targeting NF-κB Pathway for the Therapy of Diseases: Mechanism and Clinical Study. Signal Transduction and Targeted Therapy, 5, Article No. 209. [Google Scholar] [CrossRef] [PubMed]
[12] Lenardo, M.J. and Baltimore, D. (1989) NF-κB: A Pleiotropic Mediator of Inducible and Tissue-Specific Gene Control. Cell, 58, 227-229. [Google Scholar] [CrossRef] [PubMed]
[13] Mulero, M.C., Huxford, T. and Ghosh, G. (2019) NF-κB, IκB, and IKK: Integral Components of Immune System Signaling. In: Jin, T. and Yin, Q., Eds., Structural Immunology, Springer, 207-226. [Google Scholar] [CrossRef] [PubMed]
[14] Li, C., Moro, S., Shostak, K., O’Reilly, F.J., Donzeau, M., Graziadei, A., et al. (2024) Molecular Mechanism of IKK Catalytic Dimer Docking to NF-κB Substrates. Nature Communications, 15, Article No. 7692. [Google Scholar] [CrossRef] [PubMed]
[15] Deka, K. and Li, Y. (2023) Transcriptional Regulation during Aberrant Activation of NF-κB Signalling in Cancer. Cells, 12, Article 788. [Google Scholar] [CrossRef] [PubMed]
[16] Senftleben, U., Cao, Y., Xiao, G., Greten, F.R., Krähn, G., Bonizzi, G., et al. (2001) Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway. Science, 293, 1495-1499. [Google Scholar] [CrossRef] [PubMed]
[17] Ivashkiv, L.B. (2024) NF-κB as a Master Regulator of Musculoskeletal Inflammation. Nature Reviews Rheumatology, 20, 75-89.
[18] Li, Y., He, M., Zhang, M., Sun, J. and Li, S. (2016) The Nuclear Factor-κB Correlates with Increased Expression of Interleukin-6 and Promotes Progression of Gastric Carcinoma. Oncology Reports, 36, 3049-3056.
[19] 潘耀东. 外科病人手术创伤部位产生白介素-6 [J]. 国外医学∙外科学分册, 1995(5): 293.
[20] (2024) Ankle Joint Inflammation: From Molecular Mechanisms to Clinical Phenotypes. Nature Reviews Rheumatology, 20, 135-150.
[21] Esmon, C.T., Xu, J. and Lupu, F. (2011) Innate Immunity and Coagulation. Journal of Thrombosis and Haemostasis, 9, 182-188. [Google Scholar] [CrossRef] [PubMed]
[22] Sun, H., Wang, X., Degen, J.L. and Ginsburg, D. (2009) Reduced Thrombin Generation Increases Host Susceptibility to Group a Streptococcal Infection. Blood, 113, 1358-1364. [Google Scholar] [CrossRef] [PubMed]
[23] 陈婷雁. C反应蛋白与超敏C反应蛋白的检测及其临床意义分析[J]. 饮食保健, 2018, 5(50): 314.
[24] Sabaté-Brescó, M., Berset, C.M., Zeiter, S., Stanic, B., Thompson, K., Ziegler, M., et al. (2021) Fracture Biomechanics Influence Local and Systemic Immune Responses in a Murine Fracture-Related Infection Model. Biology Open, 10, bio057315. [Google Scholar] [CrossRef] [PubMed]
[25] Sproston, N.R. and Ashworth, J.J. (2018) Role of C-Reactive Protein at Sites of Inflammation and Infection. Frontiers in Immunology, 9, Article 754. [Google Scholar] [CrossRef] [PubMed]
[26] Girerd, N., Huttin, O. and Zannad, F. (2016) Echocardiography in Hypertension in the Era of Risk Stratification and Personalized Medicine. American Journal of Hypertension, 29, 792-795. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, L., Zeng, Y., Qi, J., Xu, Y., Zhang, S., Zhou, X., et al. (2018) A Cynomolgus Monkey Model of Carotid Atherosclerosis Induced by Puncturing and Scratching of the Carotid Artery Combined with a High-Fat Diet. Experimental and Therapeutic Medicine, 16, 113-120. [Google Scholar] [CrossRef] [PubMed]
[28] Muñoz, J., Akhavan, N.S., Mullins, A.P. and Arjmandi, B.H. (2020) Macrophage Polarization and Osteoporosis: A Review. Nutrients, 12, Article 2999. [Google Scholar] [CrossRef] [PubMed]
[29] 王小璐, 崔宇, 张令强. 促进骨折愈合的治疗策略及机制研究进展[J]. 生命科学, 2021, 33(1): 121-130.
[30] 刘超, 刘帆, 孟旭初, 等. 柴苓汤对闭合性多发骨折早期血清炎性因子影响的临床研究[J]. 成都中医药大学学报, 2023, 46(1): 41-45.
[31] 李良琦, 赵崇海, 王海涛, 等. 老年股骨颈骨折患者全髋关节置换手术前后血清Leptin、TNF-α、IL-6水平的变化及临床意义[J]. 中国当代医药, 2017, 24(31): 98-100.
[32] 张永, 卢奔腾, 顾文浩, 等. 新安医学流派伤科活血化瘀汤剂联合手术治疗踝关节骨折的临床研究[J]. 黑龙江医学, 2024, 48(18): 2217-2219.
[33] Standring, S. (2016) Gray’s Anatomy: The Anatomical Basis of Clinical Practice. 41st Edition, Elsevier, 1324-1326.
[34] Palumbo, A., Atzeni, F., Murdaca, G. and Gangemi, S. (2023) The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and Il-33. International Journal of Molecular Sciences, 24, Article 12143. [Google Scholar] [CrossRef] [PubMed]
[35] Stucken, C., Olszewski, D.C., Creevy, W.R., Murakami, A.M. and Tornetta, P., (2014) Analysis of Articular Cartilage Damage in Operatively Treated Ankle Fractures. Journal of Orthopaedic Trauma, 28, 314-319.
[36] 孙康, 董红华, 江磊, 等. 膝骨性关节炎患者血清和关节液中血管内皮细胞因子、白细胞介素-6、白细胞介素-8的表达与意义[J]. 现代医学与健康研究电子杂志, 2023, 7(11): 99-101.
[37] 娄本敬, 次旺, 严华韬, 等. 细胞因子在世居藏族膝骨关节炎患者血清和关节液中的表达水平[J]. 西藏医药, 2024, 45(5): 20-22.
[38] 袁红丽, 王娴, 汪秀梅, 等. 类风湿关节炎患者血清及关节液血管生成素样蛋白4、白细胞介素-17、核因子κB受体活化因子配体的临床意义[J]. 实用临床医药杂志, 2022, 26(17): 57-62.
[39] 庞永涛. 重度创伤骨折术后IL-2、IL-6动态变化及相关性研究[D]: [硕士学位论文]. 济南: 山东大学, 2005.
[40] 张舒敏, 刘维, 曾萍, 张沁凌. 白介素-6在痛风中作用的研究进展[J]. 中国现代医学杂志, 2024, 32(3): 45-52.
[41] Kwon, R.Y., Lee, K.M., Park, J.Y., et al. (2023) TNF-α/IL-1β Ratio at 72h Post-Injury Correlates with Chronic Pain Development. The Journal of Bone and Joint Surgery, 105, 1099-1110.
[42] 贾星海, 董苏伟, 段钢, 等. 膝关节运动性骨挫伤患者血清缺氧诱导因子-1α、基质金属蛋白酶-9、肿瘤坏死因子-α水平变化及其与疼痛、水肿相关性[J]. 临床军医杂志, 2025, 53(4): 406-409.
[43] Wang, Q., Chen, J., Smith, R.A., et al. (2023) Spatiotemporal Targeting of NF-κB Signaling for Chronic Inflammatory Disorders. Science Translational Medicine, 15, eabn5858.
[44] 张红梅, 宋阳, 邹明, 等. 骨科重症创伤患者血清白介素-6、肿瘤坏死因子-α、高敏C反应蛋白水平联合检测的临床价值分析[J]. 标记免疫分析与临床, 2018, 25(9): 1331-1334.
[45] 刘巧敏. 血浆纤维蛋白原、白介素-6和D-二聚体检测对髋部骨折患者围术期下肢深静脉血栓形成的诊断价值分析[J]. 河南外科学杂志, 2022, 28(4): 165-167.
[46] Gorter, E.A., van Wessem, K.J., et al. (2024) Serum IL-6/hs-CR Ptrajectory Predicts Nonunion in Ankle Fractures: A Multicenter Cohort Study. Journal of Orthopaedic Trauma, 38, e78-e85.
[47] 徐向阳, 孙军平, 李云朋, 等. IGF-1、TNF-α、NF-κB p65亚基预测胫骨平台骨折术后愈合延迟的价值[J]. 分子诊断与治疗杂志, 2021, 13(8): 1333-1336, 1340.
[48] 闻静. 血常规、生化及血清白介素-6、肿瘤坏死因子-α对骨折患者内固定术后不良事件的预测价值分析[J]. 临床研究, 2025, 33(4): 16-20.
[49] 欧双权, 陈立. 开放性骨折患者清创前、后创面细菌计数、NF-κB/JNK/PI3K炎症信号通路相关因子对骨感染的诊断价值[J]. 检验医学与临床, 2024, 21(23): 3504-3509.
[50] 刘树馨. 核因子κ-B配体受体致活剂抑制剂对糖皮质激素性骨质疏松患者骨密度及骨代谢指标的影响[J]. 大医生, 2023, 8(22): 53-55.
[51] 陈航, 高燕, 王梅. 糖皮质激素对骨密度及骨折发生的影响[J]. 中国综合临床, 2006(12): 1149-1151.
[52] 张亮. 陈志荣. 吴兴临, 等. 依那西普对钛颗粒诱导小鼠骨溶解及破骨细胞增殖的影响[J]. 中国组织工程研究与临床康复, 2008, 12(9): 1601-1604.
[53] 孙凤艳, 冯红卫, 刘振, 等. 基于TNF-α/NF-κB信号通路探讨依那西普对老年类风湿关节炎患者关节功能的影响[J]. 临床和实验医学杂志, 2025, 24(23): 2495-2499.
[54] 林静岚. 托珠单抗联合塞来昔布治疗中重度类风湿关节炎患者的疗效评估[J]. 北方药学, 2025, 22(6): 153-155.
[55] 盛学鑫, 张明师, 周子斐, 等. 踝关节骨折严重程度及预后功能与细胞因子水平的相关性分析[J]. 中华骨与关节外科杂志, 2024, 17(4): 354-360.
[56] 朱建祥, 闵继康, 胡文林, 等. 踝关节骨折术后并发不良预后的相关因素分析[J]. 浙江创伤外科, 2023, 28(10): 1935-1938.
[57] 仓挺松, 曹峰, 吴骏, 等. 基于Lasso-Logistic回归构建胫骨平台骨折术后发生创伤性关节炎的风险预警模型[J]. 安徽医学, 2025, 46(4): 431-438.

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