MMP-9/TIMP-1比值在慢性阻塞性肺疾病气道重塑中的研究进展
Research Progress of MMP-9/TIMP-1 Ratio in Airway Remodeling in Chronic Obstructive Pulmonary Disease
DOI: 10.12677/jcpm.2025.42206, PDF,    科研立项经费支持
作者: 曹梦莹, 刘思琪, 吴 楠:内蒙古民族大学临床医学院,内蒙古 通辽;佟淑平*:内蒙古民族大学附属医院呼吸与危重症医学科,内蒙古 通辽
关键词: 慢性阻塞性肺疾病气道重塑基质金属蛋白酶-9金属蛋白酶组织抑制剂-1MMP-9/TIMP-1Chronic Obstructive Pulmonary Disease Airway Remodeling Matrix Metalloproteinase-9 Tissue Inhibitor of Metalloproteinase-1 MMP-9/TIMP-1
摘要: 慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进展中的重要性。目前气道重塑的具体机制不明。临床上通过胸部CT发现的气道异常常提示患者已经发生了气道重塑,因此,寻找识别早期气道重塑的方法至关重要。研究表明,基质金属蛋白酶-9 (matrix metalloproteinase-9, MMP-9)、金属蛋白酶组织抑制剂-1 (tissue inhibitor of metalloproteinase-1, TIMP-1)、及MMP-9/TIMP-1比值之间的失衡参与COPD的气道重塑过程,本文叙述了MMP-9、TIMP-1及MMP-9/TIMP-1比值作为非侵入性诊断标志物在COPD气道重塑方面的研究进展,期待能提高人们对早期气道重塑的认知,希望能为将来气道重塑靶向药的问世尽一份绵薄之力。
Abstract: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease caused by airway inflammation and airway remodeling (AR). Among them, the positive feedback loop between airway remodeling and the progression of COPD shows the importance of airway remodeling in the progress of COPD. At present, the specific mechanism of airway remodeling is unknown. Airway abnormalities found by chest CT often indicate that airway remodeling has occurred in patients. Therefore, it is very important to find a method to identify early airway remodeling. Studies have shown that the imbalance between matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and MMP-9/TIMP-1 ratio is involved in the airway remodeling of COPD. This paper describes the research progress of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio as non-invasive diagnostic markers in airway remodeling of COPD. It is expected to improve people’s understanding of early airway remodeling and make a modest contribution to the development of targeted drugs for airway remodeling in the future.
文章引用:曹梦莹, 刘思琪, 吴楠, 佟淑平. MMP-9/TIMP-1比值在慢性阻塞性肺疾病气道重塑中的研究进展[J]. 临床个性化医学, 2025, 4(2): 495-501. https://doi.org/10.12677/jcpm.2025.42206

参考文献

[1] Cornelius, T. (2024) Clinical Guideline Highlights for the Hospitalist: GOLD COPD Update 2024. Journal of Hospital Medicine, 19, 818-820. [Google Scholar] [CrossRef] [PubMed]
[2] Wang, K., Zhao, S., Yau, S.Z., Wei, Y., Li, Y., Orr, R.W., et al. (2024) Outcomes and Hospital Service Use among Patients with COPD in a Nurse-and Allied Health-Led Clinic. JAMA Health Forum, 5, e241575. [Google Scholar] [CrossRef] [PubMed]
[3] 郭青. 基于PI3K/AKT/mTOR信号通路探讨芍药苷对慢性阻塞性肺疾病气道重塑机制的研究[D]: [硕士学位论文]. 济宁: 济宁医学院, 2024.
[4] Joe, Y.A., Lee, M.J. and Choi, H.S. (2024) Experimental Mouse Models and Human Lung Organoid Models for Studying Chronic Obstructive Pulmonary Disease. Biomolecules & Therapeutics, 32, 685-696. [Google Scholar] [CrossRef] [PubMed]
[5] 裴彩霞. 慢性阻塞性肺疾病气道重塑与病理特征的相关性研究[D]: [硕士学位论文]. 南昌: 南昌大学, 2024.
[6] Zhu, W., Han, L., Wu, Y., Tong, L., He, L., Wang, Q., et al. (2023) Keratin 15 Protects against Cigarette Smoke-Induced Epithelial Mesenchymal Transformation by MMP-9. Respiratory Research, 24, Article No. 297. [Google Scholar] [CrossRef] [PubMed]
[7] Dimic-Janjic, S., Hoda, M.A., Milenkovic, B., Kotur-Stevuljevic, J., Stjepanovic, M., Gompelmann, D., et al. (2023) The Usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 Ratio for Diagnosis and Assessment of COPD Severity. European Journal of Medical Research, 28, Article No. 127. [Google Scholar] [CrossRef] [PubMed]
[8] Li, H., Shi, K., Zhao, Y., Du, J., Hu, D. and Liu, Z. (2019) TIMP-1 and MMP-9 Expressions in COPD Patients Complicated with Spontaneous Pneumothorax and Their Correlations with Treatment Outcomes. Pakistan Journal of Medical Sciences, 36, 192-197. [Google Scholar] [CrossRef] [PubMed]
[9] 吴越. 高钙通过调控肾小管上皮细胞MMP-9表达促进肾结石形成的机制研究[D]: [博士学位论文]. 武汉: 华中科技大学, 2022.
[10] ÓLafsdóttir, I.S., Janson, C., Lind, L., Hulthe, J., Gunnbjörnsdóttir, M. and Sundström, J. (2010) Serum Levels of Matrix Metalloproteinase‐9, Tissue Inhibitors of Metalloproteinase‐1 and Their Ratio Are Associated with Impaired Lung Function in the Elderly: A Population‐based Study. Respirology, 15, 530-535. [Google Scholar] [CrossRef] [PubMed]
[11] Kang, M.J., Oh, Y.M., Lee, J.C., Kim, D.G., Park, M.J., Lee, M.G., et al. (2003) Lung Matrix Metalloproteinase-9 Correlates with Cigarette Smoking and Obstruction of Airflow. Journal of Korean Medical Science, 18, 821-827. [Google Scholar] [CrossRef] [PubMed]
[12] 张艺, 黄奋飞, 徐旭燕. 慢性阻塞性肺疾病患者血清基质金属蛋白酶-9和金属蛋白酶抑制剂-1的表达及其对肺血管重塑的预测价值[J]. 实用医学杂志, 2023, 39(7): 849-854.
[13] Wells, J.M., Parker, M.M., Oster, R.A., Bowler, R.P., Dransfield, M.T., Bhatt, S.P., et al. (2018) Elevated Circulating MMP-9 Is Linked to Increased COPD Exacerbation Risk in SPIROMICS and Copdgene. JCI Insight, 3, e123614. [Google Scholar] [CrossRef] [PubMed]
[14] Rak-Pasikowska, A., Hałucha, K., Sapa-Wojciechowska, A., Wrzyszcz, A., Gałuszka, W., Pęcak-Solińska, A., et al. (2024) The Effect of Leukocyte Removal and Matrix Metalloproteinase Inhibition on Platelet Storage Lesions. Cells, 13, Article 506. [Google Scholar] [CrossRef] [PubMed]
[15] Singh, B., Ghosh, N., Saha, D., Sarkar, S., Bhattacharyya, P. and Chaudhury, K. (2019) Effect of Doxycyline in Chronic Obstructive Pulmonary Disease—An Exploratory Study. Pulmonary Pharmacology & Therapeutics, 58, Article ID: 101831. [Google Scholar] [CrossRef] [PubMed]
[16] Jiang, J., Wang, M., Shen, W., Wu, J., Ma, Q., Wang, Z., et al. (2024) CD146 Deficiency Aggravates Chronic Obstructive Pulmonary Disease via the Increased Production of S100A9 and MMP-9 in Macrophages. International Immunopharmacology, 127, Article ID: 111410. [Google Scholar] [CrossRef] [PubMed]
[17] 冷安明, 杨静, 张葵. 桑色素通过抑制MMP9表达改善慢性阻塞性肺疾病[J]. 安徽医科大学学报, 2023, 58(12): 1987-1994.
[18] Justo, B.L. and Jasiulionis, M.G. (2021) Characteristics of TIMP1, CD63, and Β1-Integrin and the Functional Impact of Their Interaction in Cancer. International Journal of Molecular Sciences, 22, Article 9319. [Google Scholar] [CrossRef] [PubMed]
[19] Almuntashiri, S., Alhumaid, A., Zhu, Y., Han, Y., Dutta, S., Khilji, O., et al. (2023) TIMP-1 and Its Potential Diagnostic and Prognostic Value in Pulmonary Diseases. Chinese Medical Journal Pulmonary and Critical Care Medicine, 1, 67-76. [Google Scholar] [CrossRef] [PubMed]
[20] Dong, J. and Ma, Q. (2016) TIMP1 Promotes Multi-Walled Carbon Nanotube-Induced Lung Fibrosis by Stimulating Fibroblast Activation and Proliferation. Nanotoxicology, 11, 41-51. [Google Scholar] [CrossRef] [PubMed]
[21] Kolb, M., Bonniaud, P., Galt, T., Sime, P.J., Kelly, M.M., Margetts, P.J., et al. (2002) Differences in the Fibrogenic Response after Transfer of Active Transforming Growth Factor-β1 Gene to Lungs of “Fibrosis-Prone” and “Fibrosis-Resistant” Mouse Strains. American Journal of Respiratory Cell and Molecular Biology, 27, 141-150. [Google Scholar] [CrossRef] [PubMed]
[22] Arbaningsih, S.R., Syarani, F., Ganie, R.A. and Lelo, A. (2019) The Levels of Vitamin D, Metalloproteinase-9 and Tissue Inhibitor Metalloproteinase-1 in COPD Patients, Healthy Smokers and Non-Smokers of Indonesian Citizens. Open Access Macedonian Journal of Medical Sciences, 7, 2123-2126. [Google Scholar] [CrossRef] [PubMed]
[23] Mancuso, P. and Bouchard, B. (2019) The Impact of Aging on Adipose Function and Adipokine Synthesis. Frontiers in Endocrinology, 10, Article 137. [Google Scholar] [CrossRef] [PubMed]
[24] Wang, L., Zhang, C., Jia, Y. and Hu, L. (2020) Tissue Inhibitor of Metalloprotease-1 (TIMP-1) Regulates Adipogenesis of Adipose-Derived Stem Cells (ASCs) via the Wnt Signaling Pathway in an MMP-Independent Manner. Current Medical Science, 40, 989-996. [Google Scholar] [CrossRef] [PubMed]
[25] Uysal, P. and Uzun, H. (2019) Relationship between Circulating Serpina3g, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinase-1 and-2 with Chronic Obstructive Pulmonary Disease Severity. Biomolecules, 9, Article 62. [Google Scholar] [CrossRef] [PubMed]
[26] 徐梦娇, 王海强, 汪伟, 等. 中医药干预慢性阻塞性肺疾病蛋白酶-抗蛋白酶失衡机制的研究进展[J]. 世界中医药, 2024, 19(10): 1500-1504, 1509.
[27] Gilowska, I., Kasper, Ł., Bogacz, K., Szczegielniak, J., Szymasek, T., Kasper, M., et al. (2018) Impact of Matrix Metalloproteinase 9 on COPD Development in Polish Patients: Genetic Polymorphism, Protein Level, and Their Relationship with Lung Function. BioMed Research International, 2018, Article ID: 6417415. [Google Scholar] [CrossRef] [PubMed]
[28] Shen, D., Yang, Z., Huang, J., Yang, F., Lin, Z., Ou, Y., et al. (2019) Liuweibuqi Capsules Improve Pulmonary Function in Stable Chronic Obstructive Pulmonary Disease with Lung-Qi Deficiency Syndrome by Regulating STAT4/STAT6 and MMP-9/TIMP-1. Pharmaceutical Biology, 57, 744-752. [Google Scholar] [CrossRef] [PubMed]