文献类型：期刊文献

英文题名：Chronic Hypobaric Hypoxia at High Altitudes Aggravates Chronic Obstructive Pulmonary Disease in Mice

作者：Huang, Yuhang[1,2,3,4,5,6];Hei, Xiancheng[7,8];Fu, Xiang[7];Ma, Linxi[1,2,3,4,5,6];Chen, Yiling[2,3,4,5,6];Zhang, Yi[7];Wang, Yunchao[9];Duan, Ruirui[2,3,4,5,6];Wang, Xinhua[7];Yang, Ting[1,2,3,4,5,6]

第一作者：Huang, Yuhang

通信作者：Yang, T[1];Yang, T[2];Yang, T[3];Yang, T[4];Yang, T[5];Yang, T[6];Wang, XH[7]

机构：[1]Chinese Acad Med Sci & Peking Union Med Coll, China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China;[2]China Japan Friendship Hosp, Ctr Resp Med, Dept Pulm & Crit Care Med, Beijing, Peoples R China;[3]Chinese Acad Med Sci, Natl Ctr Resp Med, Beijing, Peoples R China;[4]Chinese Acad Med Sci, State Key Lab Resp Hlth & Multimorbid, Beijing, Peoples R China;[5]Chinese Acad Med Sci, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China;[6]Chinese Acad Med Sci, Inst Resp Med, Beijing, Peoples R China;[7]Gansu Univ Tradit Chinese Med, Sch Publ Hlth, Lanzhou, Gansu, Peoples R China;[8]First Peoples Hosp Baiyin, Dept Resp & Crit Care Med, Baiyin, Gansu, Peoples R China;[9]Gansu Univ Tradit Chinese Med, Sch Basic Med Sci, Lanzhou, Gansu, Peoples R China

第一机构：Chinese Acad Med Sci & Peking Union Med Coll, China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China;[2]corresponding author), China Japan Friendship Hosp, Ctr Resp Med, Dept Pulm & Crit Care Med, Beijing, Peoples R China;[3]corresponding author), Chinese Acad Med Sci, Natl Ctr Resp Med, Beijing, Peoples R China;[4]corresponding author), Chinese Acad Med Sci, State Key Lab Resp Hlth & Multimorbid, Beijing, Peoples R China;[5]corresponding author), Chinese Acad Med Sci, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China;[6]corresponding author), Chinese Acad Med Sci, Inst Resp Med, Beijing, Peoples R China;[7]corresponding author), Gansu Univ Tradit Chinese Med, Sch Publ Hlth, Lanzhou, Gansu, Peoples R China.|[10735e9d5e7087247e71b]甘肃中医药大学公共卫生学院;[10735]甘肃中医药大学;

年份：2026

卷号：19

外文期刊名：JOURNAL OF INFLAMMATION RESEARCH

收录：;Scopus(收录号：2-s2.0-105049332571);WOS:【SCI-EXPANDED(收录号:WOS:001868736400001)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (Grant No. U24A20644, 82300051 and 82300052).

语种：英文

外文关键词：chronic obstructive pulmonary disease; chronic hypobaric hypoxia; inflammatory response; immune response; Cstdc4

摘要：Objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. However, the effects of chronic hypobaric hypoxia on COPD in high-altitude areas remain controversial. This study aimed to evaluate the impact of chronic hypobaric hypoxia on COPD in high-altitude areas. Methods: C57BL/6J mice were randomized into the sham control (MOCK; intranasal PBS), cigarette smoke extract/lipopolysaccharide (CSE/LPS, CL; intranasal CSE five times/week and LPS twice/week), chronic hypobaric hypoxia (Hy; hypobaric hypoxia at simulated 4000 meters with intranasal PBS), and chronic hypobaric hypoxia plus CL (HyCL; CSE/LPS plus chronic hypobaric hypoxia) groups for 12 weeks. After 12 weeks, pulmonary function, bronchoalveolar lavage fluid cell counts, and pulmonary histopathology were assessed. To elucidate the effects of chronic hypobaric hypoxia on COPD, we performed RNA sequencing on lung tissues to profile molecular alterations and validated key targets using qPCR and Western blotting. Results: The results indicate that chronic hypobaric hypoxia promotes COPD progression, characterized by exacerbated pulmonary function decline, emphysema, as well as small airway remodeling. Transcriptome analysis reveals that "chemical carcinogenesis- reactive oxygen species" and "extracellular matrix-receptor interactions" are common transcriptomic characteristics of COPD both with and without chronic hypobaric hypoxia exposure, whereas inflammatory and immune responses are major transcriptomic signatures driven by chronic hypobaric hypoxia. Furthermore, our results identify Cstdc4 as a key differentially expressed gene (DEG) implicated in COPD progression under chronic hypobaric hypoxia. Conclusion: These results indicate that chronic hypobaric hypoxia in high-altitude areas promotes COPD progression and correlates with a transcriptomic signature marked predominantly by the activation of inflammatory and immune responses.