实用医学杂志 ›› 2026, Vol. 42 ›› Issue (8): 1407-1414.doi: 10.3969/j.issn.1006-5725.2026.08.014

• 论著·机制探索 • 上一篇    

Sugen低氧诱导肺动脉高压小鼠模型中免疫细胞亚群的动态变化

刘杰1,薛鑫2,郭煜1,高振强1,张寒晓1,张牧之1,隆寰宇3,吕佳璐1,许蒙雨1,贾玉峰1,崔烨1,王炜1,孙英1,王蕾2()   

  1. 1.首都医科大学基础医学院免疫学系 (北京 100069 )
    2.西安交通大学第二附属医院呼吸与危重症医学科 (陕西 西安 710004 )
    3.北京大学第三医院呼吸与危重症医学科 (北京 100191 )
  • 收稿日期:2025-11-06 出版日期:2026-04-25 发布日期:2026-04-28
  • 通讯作者: 王蕾 E-mail:wl860806wb@163.com
  • 基金资助:
    国家自然科学基金项目(82202014);北京市教育委员会科研计划一般项目(KM202310025029);临港实验室“求索杰出青年计划”开放课题(LG-QS-202205-08)

Dynamic changes of immune cell subsets in a mouse model of Sugen-hypoxia-induced pulmonary hypertension

Jie LIU1,Xin XUE2,Yu GUO1,Zhenqiang GAO1,Hanxiao ZHANG1,Muzhi ZHANG1,Huanyu LONG3,Jialu LÜ1,Mengyu XU1,Yufeng JIA1,Ye CUI1,Wei WANG1,Ying SUN1,Lei WANG2()   

  1. 1.Department of Immunology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,Beijing,China
    2.Department of Respiratory and Critical Care Medicine,the Second Affiliated Hospital of Xi'an Jiaotong University,Shaanxi 710004,Xi'an,China
    3Department of Respiratory and Critical Care Medicine,Peking University Third Hospital,Beijing 100191,Beijing,China
  • Received:2025-11-06 Online:2026-04-25 Published:2026-04-28
  • Contact: Lei WANG E-mail:wl860806wb@163.com

摘要:

目的 探讨Sugen低氧(Sugen-hypoxia,SuHx)诱导的肺动脉高压(pulmonary hypertension,PH)小鼠模型中免疫细胞亚群的动态变化。 方法 建立SuHx-PH小鼠模型(皮下注射Sugen5416后联合低氧处理),分别于建模前及建模后1(h1w)、2(h2w)、3(h3w)、4(h4w)周收集小鼠肺组织,采用流式细胞术检测CD45+免疫细胞中T细胞、B细胞、巨噬细胞、嗜酸性粒细胞(EOS)、中性粒细胞(Neu)、自然杀伤(NK)细胞及固有淋巴细胞(ILC)等免疫细胞亚群的比例变化。 结果 与对照组相比,SuHx模型小鼠免疫细胞亚群呈现显著时序性变化。其中,CD11c+F4/80+总巨噬细胞、间质巨噬细胞(IM,SIGLECF?)随着建模时间的持续呈现显著的下降趋势;肺泡巨噬细胞(AM,SIGLECF+)的细胞水平持续上升(P < 0.05);EOS、ILC、Neu以及CD4+T细胞呈现显著的波动趋势,组间比较差异有统计学意义(P < 0.05)。 结论 SuHx-PH 小鼠肺组织内免疫细胞亚群比例呈现显著时序性改变,提示不同免疫细胞在PH病程发展中可能发挥阶段特异性作用:早期Neu启动急性炎症反应,EOS发挥抗炎保护作用,巨噬细胞亚群发生表型转换;中期 适应性免疫激活,CD4+T细胞参与血管重构调控,巨噬细胞进一步推动纤维化微环境形成;晚期Neu再次升高加剧炎症恶化,EOS保护作用减弱,ILC促进血管闭塞性病变。本研究为深入理解PH 免疫炎症机制及寻找潜在免疫干预靶点提供了依据。

关键词: Sugen低氧模型, 肺动脉高压, 免疫细胞, 流式细胞术

Abstract:

Objective To investigate the dynamic changes of immune cell subsets in a mouse model of pulmonary hypertension (PH) induced by Sugen-hypoxia (SuHx). Methods A SuHx-PH mouse model was established through intraperitoneal injection of Sugen 5416, followed by exposure to hypoxia. Mouse lung tissues were collected prior to modeling and at 1 week (h1w), 2 weeks (h2w), 3 weeks (h3w), and 4 weeks (h4w) post-modeling. Flow cytometry was employed to detect the proportional alterations of immune cell subsets (including T cells, B cells, macrophages, eosinophils (EOS), neutrophils (Neu), natural killer (NK) cells, and innate lymphoid cells (ILCs) within CD45+ immune cells. Results Compared with the control group, the immune cell subsets in SuHx model mice demonstrated significant temporal changes. Among these, the total CD11c+F4/80+ macrophages and interstitial macrophages (IM, SIGLECF-) showed a significant decreasing tendency as the modeling time progressed; the cell levels of alveolar macrophages (AM, SIGLECF+) continuously increased (P < 0.05); EOS, ILCs, Neu, and CD4+T cells displayed a significant fluctuating pattern, with significant differences between groups (P < 0.05). Conclusions The proportions of immune cell subsets in the lung tissues of SuHx-PH mice exhibit significant temporal changes, indicating that different immune cells may play stage-specific roles in the progression of PH. This study offers a foundation for a more in-depth understanding of the immunoinflammatory mechanism of PH and the identification of potential immune intervention targets.

Key words: Sugen-hypoxia model, pulmonary hypertension, immune cells, flow cytometry

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