慢性阻塞性肺疾病合并肺动脉高压相关生物标志物研究进展
Research Progress on Biomarkers of Chronic Obstructive Pulmonary Disease-Associated Pulmonary Hypertension
DOI: 10.12677/acm.2025.15123618, PDF,   
作者: 夏应婷, 柯云焯, 蔡晓玥:大理大学临床医学院,云南 大理;冷 静*:云南省第三人民医院呼吸与危重症学科,云南 昆明
关键词: 慢性阻塞性肺疾病肺动脉高压生物标志物Chronic Obstructive Pulmonary Disease Pulmonary Hypertension Biomarkers
摘要: 慢性阻塞性肺疾病(COPD)是以持续性呼吸道症状和不可逆性气流受限为主要特征的慢性肺部疾病;肺动脉高压(PH)是其中一种常见并发症,高达90%的慢性阻塞性肺疾病全球倡议(GOLD) 4期患者的平均肺动脉压(mPAP)大于20 mmHg,COPD中PH的存在与发病率、死亡率增加相关,因此,对于慢性阻塞性肺疾病合并肺动脉高压的患者,尽早发现、及时诊断、早干预,是延长其生存时间、提升生活质量的关键。本文就慢性阻塞性肺疾病合并肺动脉高压相关生物标志物的最新研究进展做一综述,以期为临床实践提供参考。
Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by persistent respiratory symptoms and irreversible airflow limitation; pulmonary hypertension (PH) is a common complication, with up to 90% of GOLD stage 4 patients having a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg. The presence of PH in COPD is associated with increased morbidity and mortality. Therefore, for patients with chronic obstructive pulmonary disease complicated by pulmonary hypertension, early detection, timely diagnosis, and early intervention are crucial to extending their survival and improving their quality of life. This article reviews the latest research progress on biomarkers related to COPD-associated PH, aiming to provide references for clinical practice.
文章引用:夏应婷, 柯云焯, 蔡晓玥, 冷静. 慢性阻塞性肺疾病合并肺动脉高压相关生物标志物研究进展[J]. 临床医学进展, 2025, 15(12): 1988-1996. https://doi.org/10.12677/acm.2025.15123618

参考文献

[1] de Oca, M.M., Perez-Padilla, R., Celli, B., Aaron, S.D., Wehrmeister, F.C., Amaral, A.F.S., et al. (2025) The Global Burden of COPD: Epidemiology and Effect of Prevention Strategies. The Lancet Respiratory Medicine, 13, 709-724. [Google Scholar] [CrossRef] [PubMed]
[2] Mekov, E.V., Yanev, N.A., Kurtelova, N., Mihalova, T., Tsakova, A., Yamakova, Y., et al. (2025) Phenotyping Chronic Obstructive Pulmonary Disease through Principal Component Analysis: Identification of Clinical Clusters. Cureus, 17, e82811. [Google Scholar] [CrossRef] [PubMed]
[3] Wells, J.M., Morrison, J.B., Bhatt, S.P., Nath, H. and Dransfield, M.T. (2016) Pulmonary Artery Enlargement Is Associated with Cardiac Injury during Severe Exacerbations of COPD. Chest, 149, 1197-1204. [Google Scholar] [CrossRef] [PubMed]
[4] 韦兰雅, 梁毅, 孙雪皎, 等. 中性粒细胞与淋巴细胞比值在慢性阻塞性肺疾病合并肺癌中的相关研究进展[J/OL]. 细胞与分子免疫学杂志, 1-13.
https://kns.cnki.net/kcms2/article/abstract?v=RPbSoBw3VsEVo08vniej7r3FcRL1EzK0ZJP5kF4CZUqSO_jqmChFdJ4hcD5YpH8izV1BPOoQV14FLYVBZyA1I7t9YHRQ0AAvmYZAlLd-VsCw2TNXVU6HDiYKgI6HlFpLzcNwyl2CTdoe_elm6DxI_RzprZEgenacOhSLyPkEawAGY9ro2jzwzWD9MX5Fk7iXQVDFNZAoz10=&uniplatform=NZKPT&language=CHS, 2025-11-13.
[5] 张芝瑞, 张艳, 李俊杰, 等. 慢性阻塞性肺疾病并发肺动脉高压患者血清微小RNA-130a、中性粒细胞与淋巴细胞比值、胸部血管CT参数变化及其与病情程度关系研究[J]. 陕西医学杂志, 2024, 53(12): 1640-1644.
[6] Jiang, T., Wang, Q., Zhang, Z., Qi, J., Yang, Z., Jiang, Q., et al. (2023) Value of the Neutrophil-to-Lymphocyte Ratio in Chronic Obstructive Pulmonary Disease Complicated with Pulmonary Hypertension. Journal of International Medical Research, 51, 1-10.
[7] 相辉艳, 庞敏. 慢性阻塞性肺疾病患者炎症指标变化与肺动脉高压的关系[J]. 实用医院临床杂志, 2025, 22(2): 159-162.
[8] 宋玉良, 王永. 慢性阻塞性肺疾病急性加重患者外周血红细胞分布宽度、嗜酸性粒细胞、B型钠尿肽的诊断价值及相关性分析[J]. 分子诊断与治疗杂志, 2024, 16(5): 890-893+903.
[9] 陈明明, 昌淑婷, 朱磊, 等. 红细胞分布宽度与白蛋白比值对慢性阻塞性肺疾病急性加重期患者出院后1年内再入院的预测价值[J]. 临床肺科杂志, 2025, 30(5): 732-738.
[10] Yang, J., Liu, C., Li, L., Tu, X. and Lu, Z. (2019) Red Blood Cell Distribution Width Predicts Pulmonary Hypertension Secondary to Chronic Obstructive Pulmonary Disease. Canadian Respiratory Journal, 2019, Article ID: 3853454. [Google Scholar] [CrossRef] [PubMed]
[11] 高笑宇, 刘柯含, 云春梅. 血小板活化因子在慢阻肺合并肺动脉高压中的诊断价值[J]. 内蒙古医科大学学报, 2022, 44(1): 15-19.
[12] Minai, O.A., Chaouat, A. and Adnot, S. (2010) Pulmonary Hypertension in COPD: Epidemiology, Significance, and Management: Pulmonary Vascular Disease; The Global Perspective. Chest, 137, 39S-51S. [Google Scholar] [CrossRef] [PubMed]
[13] 徐明艳, 韩校鹏, 刘英丽, 等. 慢性阻塞性肺疾病急性加重期并发肺动脉高压的危险因素[J]. 实用医学杂志, 2022, 38(19): 2467-2471.
[14] 刘超龙. 纤维蛋白原、D-二聚体水平联合检测在慢性阻塞性肺疾病急性加重期患者细菌感染诊断中的效能[J/OL]. 中国典型病例大全, 1-7.
https://kns.cnki.net/kcms2/article/abstract?v=X84Xx1LLloK6k-mgiTX8L4v3mPHbmNVLKO4NMBA2UmCJ-rnSXWDI7gMRltvMKYH_pxyEfauUws8JGpuCSgyywpyaDk8xhn--JnApKilszuC_jHK7s1XnN89mlfxi-afQTaQdMaiOEV3ddcVsYcyFi69uxtdXQtVAkp_S5l2VwlWKtvyYkYAdbP6O81l-zWclcjDWCmMkdiI=&uniplatform=NZKPT, 2025-10-31.
[15] 李冬云. 慢性阻塞性肺疾病凝血功能和血气分析相关性的研究[J]. 临床肺科杂志, 2013, 18(11): 2023-2025.
[16] 武红莉, 田瑞雪, 叶青, 等. B型脑钠肽、超敏C反应蛋白、纤维蛋白原、D-二聚体及血气分析在慢性阻塞性肺疾病急性加重期合并肺动脉高压患者中的表达[J]. 实用临床医药杂志, 2018, 22(3): 31-33+37.
[17] 梁雅雪, 范晓云, 江子丰, 等. 止凝血功能对于慢性阻塞性肺疾病急性加重期合并肺动脉高压患者的临床意义[J]. 中国临床保健杂志, 2019, 22(2): 200-204.
[18] 曹秀丽, 焦建华, 张智慧, 等. 慢阻肺并发肺动脉高压患者血清CRP、IL-6和TLR4的差异表达及相关性分析[J]. 标记免疫分析与临床, 2019, 26(4): 645-649.
[19] Phillips, K.M., Lavere, P.F., Hanania, N.A. and Adrish, M. (2025) The Emerging Biomarkers in Chronic Obstructive Pulmonary Disease: A Narrative Review. Diagnostics, 15, Article No. 1245. [Google Scholar] [CrossRef] [PubMed]
[20] Ma, Q., et al. (2023) Purine Synthesis Suppression Reduces the Development and Progression of Pulmonary Hypertension in Rodent Models. European Heart Journal, 44, 1265-1279.
[21] Enrico, G., Francesco, M., Roberta, F., et al. (2023) Inhibiting IL-6 in Medicine; a New Twist to Sustain Inhibition of His Cytokine Tin the Therapy of Pulmonary Arterial Hypertension. Pharmacological Research, 192, Article ID: 106750.
[22] Swaroop, A.K., Negi, P., Kar, A., Mariappan, E., Natarajan, J., Namboori P.K., K., et al. (2024) Navigating IL-6: From Molecular Mechanisms to Therapeutic Breakthroughs. Cytokine & Growth Factor Reviews, 76, 48-76. [Google Scholar] [CrossRef] [PubMed]
[23] 陈新乐, 张涛, 黄淑君. COPD合并肺动脉高压患者血清IL-6、B型利钠肽水平变化及意义[J]. 中国卫生工程学, 2024, 23(5): 712-713+716.
[24] Ulrike, F., Yvonne, R., Marion, S., et al. (2006) Angiopoietin-2 Sensitizes Endothelial Cells to TNF-Alpha and Has a Crucial Role in the Induction of Inflammation. Nature Medicine, 12, 235-239.
[25] Ni, R., Xie, M., Zhang, J. and Zhong, M. (2025) Expression and Predictive Value of Angiopoietin-2 in Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease. COPD: Journal of Chronic Obstructive Pulmonary Disease, 22, 2512749. [Google Scholar] [CrossRef] [PubMed]
[26] Cero, F.T., Hillestad, V., Sjaastad, I., Yndestad, A., Aukrust, P., Ranheim, T., et al. (2015) Absence of the Inflammasome Adaptor ASC Reduces Hypoxia-Induced Pulmonary Hypertension in Mice. American Journal of Physiology-Lung Cellular and Molecular Physiology, 309, L378-L387. [Google Scholar] [CrossRef] [PubMed]
[27] Parpaleix, A., Amsellem, V., Houssaini, A., Abid, S., Breau, M., Marcos, E., et al. (2016) Role of Interleukin-1 Receptor 1/MyD88 Signalling in the Development and Progression of Pulmonary Hypertension. European Respiratory Journal, 48, 470-483. [Google Scholar] [CrossRef] [PubMed]
[28] Itoh, A., Nishihira, J., Makita, H., Miyamoto, K., Yamaguchi, E. and Nishimura, M. (2003) Effects of IL-1beta, TNF-alpha, and Macrophage Migration Inhibitory Factor on Prostacyclin Synthesis in Rat Pulmonary Artery Smooth Muscle Cells. Respirology, 8, 467-472. [Google Scholar] [CrossRef] [PubMed]
[29] Gredic, M., Blanco, I., Kovacs, G., Helyes, Z., Ferdinandy, P., Olschewski, H., et al. (2020) Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease. British Journal of Pharmacology, 178, 132-151. [Google Scholar] [CrossRef] [PubMed]
[30] Sutendra, G., Dromparis, P., Bonnet, S., Haromy, A., McMurtry, M.S., Bleackley, R.C., et al. (2011) Pyruvate Dehydrogenase Inhibition by the Inflammatory Cytokine TNFα Contributes to the Pathogenesis of Pulmonary Arterial Hypertension. Journal of Molecular Medicine, 89, 771-783. [Google Scholar] [CrossRef] [PubMed]
[31] Chen, Y.R., Leung, J.M. and Sin, D.D. (2016) A Systematic Review of Diagnostic Biomarkers of COPD Exacerbation. PLOS ONE, 11, e0158843. [Google Scholar] [CrossRef] [PubMed]
[32] Kano, K., Sakamaki, K., Oue, N., Kimura, Y., Hashimoto, I., Hara, K., et al. (2019) Impact of the esm-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy. In Vivo, 34, 461-467. [Google Scholar] [CrossRef] [PubMed]
[33] Sun, H.L., et al. (2022) Increasing Circulating ESM-1 and Adhesion Molecules Are Associated with Early-Stage Atherosclerosis in OSA Patients; A Cross-Sectional Study. Sleep Medicine, 98, 114-120.
[34] 戴国明, 朱宗成, 严力远, 等. 内皮细胞特异性分子-1对急性ST段抬高型心肌梗死患者的临床意义[J]. 当代医学, 2023, 29(27): 100-103.
[35] 栗慧, 谢梅, 闫金芳. 血清ESM-1和MCP-1预测慢性阻塞性肺疾病急性加重期并发肺动脉高压的临床效能[J]. 临床误诊误治, 2024, 37(19): 38-42.
[36] Liu, Y., Xu, K., Xiang, Y., Ma, B., Li, H., Li, Y., et al. (2024) Role of MCP-1 as an Inflammatory Biomarker in Nephropathy. Frontiers in Immunology, 14, Article ID: 1303076. [Google Scholar] [CrossRef] [PubMed]
[37] Huang, S.J., Ding, Z.N., Xiang, H.X., Fu, L. and Fei, J. (2020) Association between Serum S100A8/S100A9 Heterodimer and Pulmonary Function in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Lung, 198, 645-652. [Google Scholar] [CrossRef] [PubMed]
[38] 柴景伟, 薛洪刚, 李丹. 慢性阻塞性肺疾病患者血清Clara细胞蛋白-16和单核细胞趋化蛋白-1的表达与病情严重程度的相关性分析[J]. 临床和实验医学杂志, 2023, 22(18): 1946-1950.
[39] 陈怿, 邱嘉玲, 丁程佳, 等. 单核-巨噬细胞TREM-1对重症中暑大鼠急性肺损伤的作用及机制[J]. 解放军医学杂志, 2020, 45(1): 62-67.
[40] Guo, H., Jiang, F., Chen, C., Shi, J. and Zhao, Y. (2021) Plasma Brain Natriuretic Peptide, Platelet Parameters, and Cardiopulmonary Function in Chronic Obstructive Pulmonary Disease. World Journal of Clinical Cases, 9, 11165-11172. [Google Scholar] [CrossRef] [PubMed]
[41] Kovacs, G., Avian, A., Bachmaier, G., Troester, N., Tornyos, A., Douschan, P., et al. (2022) Severe Pulmonary Hypertension in COPD: Impact on Survival and Diagnostic Approach. Chest, 162, 202-212. [Google Scholar] [CrossRef] [PubMed]
[42] Han, K., Shi, D., Yang, L., Xie, M., Wang, Z., Gao, F., et al. (2022) Association of B-Type Natriuretic Peptide with Rapid Progression in Patients with Aortic Stenosis. Reviews in Cardiovascular Medicine, 23, Article No. 75. [Google Scholar] [CrossRef] [PubMed]
[43] Rao, S., Daines, B., Hosseini, O., Test, V. and Nugent, K. (2022) The Utility of Brain Natriuretic Peptide in Patients Undergoing an Initial Evaluation for Pulmonary Hypertension. Journal of Community Hospital Internal Medicine Perspectives, 12, 48-52. [Google Scholar] [CrossRef] [PubMed]
[44] 邹勋, 唐晓红, 景达, 等. 慢性阻塞性肺病患者并发肺动脉高压的危险因素Meta分析[J]. 重庆医学, 2024, 53(11): 1711-1716.
[45] 邓晔, 李艳, 王荣, 等. 硒蛋白P在慢性阻塞性肺疾病急性加重合并肺动脉高压患者血清中的表达和意义[J]. 临床内科杂志, 2025, 42(8): 673-675.
[46] Martens, P., Yu, S., Larive, B., Borlaug, B.A., Erzurum, S.C., Farha, S., et al. (2023) Iron Deficiency in Pulmonary Vascular Disease: Pathophysiological and Clinical Implications. European Heart Journal, 44, 1979-1991. [Google Scholar] [CrossRef] [PubMed]
[47] Hartmann, J.P., Bailey, D.M. and Berg, R.M.G. (2023) A Song of Iron and Oxygen: Hypoxic Pulmonary Vasoconstriction and Gas Exchange in Chronic Obstructive Pulmonary Disease. Experimental Physiology, 108, 535-538. [Google Scholar] [CrossRef] [PubMed]
[48] Naito, Y., Hosokawa, M., Sawada, H., Oboshi, M., Hirotani, S., Iwasaku, T., et al. (2015) Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling. American Journal of Hypertension, 29, 713-718. [Google Scholar] [CrossRef] [PubMed]
[49] Myronenko, O., Curcic, P., Douschan, P., Zeder, K., John, T., Suessner, S., et al. (2025) Soluble Transferrin Receptor-1 in Pulmonary Hypertension Associated with COPD. Lung, 203, Article No. 79. [Google Scholar] [CrossRef] [PubMed]
[50] Hsu, W., Lin, Y., Jeng, J., Chang, H. and Chou, T. (2018) Baicalein Ameliorates Pulmonary Arterial Hypertension Caused by Monocrotaline through Downregulation of ET-1 and ETAR in Pneumonectomized Rats. The American Journal of Chinese Medicine, 46, 769-783. [Google Scholar] [CrossRef] [PubMed]
[51] Chester, A.H. and Yacoub, M.H. (2014) The Role of Endothelin-1 in Pulmonary Arterial Hypertension. Global Cardiology Science and Practice, 2014, Article No. 29. [Google Scholar] [CrossRef] [PubMed]
[52] Mazurek, J.A., Jabuonski, T. and Zolty, R. (2012) Endothelin-1 Levels in COPD-Induced Pulmonary Hypertension. Journal of Cardiac Failure, 18, S29. [Google Scholar] [CrossRef
[53] Yang, D., Wang, L., Jiang, P., Kang, R. and Xie, Y. (2022) Correlation between hs-CRP, IL-6, IL-10, ET-1, and Chronic Obstructive Pulmonary Disease Combined with Pulmonary Hypertension. Journal of Healthcare Engineering, 2022, Article ID: 3247807. [Google Scholar] [CrossRef] [PubMed]
[54] Chen, Y.-R., Dai, A.-G., Hu, R.-C., et al. (2012) The Expression of Hypoxia-Inducible Factor-1alpha and Its Hydroxylases in Pulmonary Arteries of Patient with Chronic Obstructive Pulmonary Disease. Chinese Journal of Applied Physiology, 28, 234-238.
[55] Zhang, X., Zhou, Y. and Zhang, H. (2024) Clinical Significance of HIF-1α, ET-1, and NO as Biomarkers in Chronic Obstructive Pulmonary Disease Patients with Pulmonary Hypertension. Biomolecules and Biomedicine, 25, 1389-1395. [Google Scholar] [CrossRef] [PubMed]