{"title":"狼疮易感小鼠间歇性缺氧肺动脉高压模型的建立:功能、生化和组织学验证。","authors":"Dengfeng Wu, Jiangbiao Xiong, Yiping Huang, Yue Yuan, Shunjia Xing, Rui Wu","doi":"10.1080/10641963.2025.2500383","DOIUrl":null,"url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmonary arterial remodeling in SLE-PAH using MRL/lpr lupus-prone mouse. In this study, twelve female MRL/lpr mice and six female BALB/c mice were exposed to hypoxia for 2 hours daily over 28 days in a hypoxic chamber (FiO₂, 12%). Among them, six MRL/lpr mice received treatment with LW6, a HIF-1α inhibitor. Moreover, six MRL/lpr mice were exposed to normoxia (FiO2, 21%) and served as controls. As a result, IH MRL/lpr mice developed significant PAH, with right ventricular systolic pressure (RVSP) measuring 32.95 ± 2.08 mmHg, significantly higher than the 26.63 ± 2.72 mmHg observed in normoxic MRL/lpr mice (<i>p</i> < .001). Additionally, the right ventricular hypertrophy index (RVHI) and medial wall thickness (MWT) of pulmonary artery markedly elevated in IH MRL/lpr mice. The protein expression level of HIF-1a and P-NFκB were significantly upregulated in the lungs of these mice. However, treatment with LW6 during hypoxia reduced RVSP and alleviated pulmonary arterial remodeling in MRL/lpr mice. Notably, BALB/c mice subjected to 2 hours of daily hypoxia did not exhibit pulmonary arterial remodeling. This study establishes a reproducible SLE-PAH model, demonstrates the critical role of hypoxia in disease progression, and identifies HIF-1α as a potential therapeutic target for managing SLE-PAH.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"47 1","pages":"2500383"},"PeriodicalIF":1.5000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications.\",\"authors\":\"Dengfeng Wu, Jiangbiao Xiong, Yiping Huang, Yue Yuan, Shunjia Xing, Rui Wu\",\"doi\":\"10.1080/10641963.2025.2500383\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmonary arterial remodeling in SLE-PAH using MRL/lpr lupus-prone mouse. In this study, twelve female MRL/lpr mice and six female BALB/c mice were exposed to hypoxia for 2 hours daily over 28 days in a hypoxic chamber (FiO₂, 12%). Among them, six MRL/lpr mice received treatment with LW6, a HIF-1α inhibitor. Moreover, six MRL/lpr mice were exposed to normoxia (FiO2, 21%) and served as controls. As a result, IH MRL/lpr mice developed significant PAH, with right ventricular systolic pressure (RVSP) measuring 32.95 ± 2.08 mmHg, significantly higher than the 26.63 ± 2.72 mmHg observed in normoxic MRL/lpr mice (<i>p</i> < .001). Additionally, the right ventricular hypertrophy index (RVHI) and medial wall thickness (MWT) of pulmonary artery markedly elevated in IH MRL/lpr mice. The protein expression level of HIF-1a and P-NFκB were significantly upregulated in the lungs of these mice. However, treatment with LW6 during hypoxia reduced RVSP and alleviated pulmonary arterial remodeling in MRL/lpr mice. Notably, BALB/c mice subjected to 2 hours of daily hypoxia did not exhibit pulmonary arterial remodeling. This study establishes a reproducible SLE-PAH model, demonstrates the critical role of hypoxia in disease progression, and identifies HIF-1α as a potential therapeutic target for managing SLE-PAH.</p>\",\"PeriodicalId\":10333,\"journal\":{\"name\":\"Clinical and Experimental Hypertension\",\"volume\":\"47 1\",\"pages\":\"2500383\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Hypertension\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10641963.2025.2500383\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Hypertension","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10641963.2025.2500383","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/2 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications.
Pulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmonary arterial remodeling in SLE-PAH using MRL/lpr lupus-prone mouse. In this study, twelve female MRL/lpr mice and six female BALB/c mice were exposed to hypoxia for 2 hours daily over 28 days in a hypoxic chamber (FiO₂, 12%). Among them, six MRL/lpr mice received treatment with LW6, a HIF-1α inhibitor. Moreover, six MRL/lpr mice were exposed to normoxia (FiO2, 21%) and served as controls. As a result, IH MRL/lpr mice developed significant PAH, with right ventricular systolic pressure (RVSP) measuring 32.95 ± 2.08 mmHg, significantly higher than the 26.63 ± 2.72 mmHg observed in normoxic MRL/lpr mice (p < .001). Additionally, the right ventricular hypertrophy index (RVHI) and medial wall thickness (MWT) of pulmonary artery markedly elevated in IH MRL/lpr mice. The protein expression level of HIF-1a and P-NFκB were significantly upregulated in the lungs of these mice. However, treatment with LW6 during hypoxia reduced RVSP and alleviated pulmonary arterial remodeling in MRL/lpr mice. Notably, BALB/c mice subjected to 2 hours of daily hypoxia did not exhibit pulmonary arterial remodeling. This study establishes a reproducible SLE-PAH model, demonstrates the critical role of hypoxia in disease progression, and identifies HIF-1α as a potential therapeutic target for managing SLE-PAH.
期刊介绍:
Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions.
One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field.
The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.