Huang Jianmin, He Shan, Zhang Qiuyun, Liu Yunliang, You Yongjing
Department of Otorhinolaryngology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350011, Fujian, China.
Department of Otorhinolaryngology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Eur J Med Res. 2025 Aug 23;30(1):794. doi: 10.1186/s40001-025-03080-7.
Hypoxia can impair cell and organ function, and cause apoptosis and various diseases. At present, there are many studies on pulmonary hypoxia but few studies on bronchial injury. The study aimed to research the impact of hypoxia on the barrier function of human bronchial epithelial cells and the expression level of tight junction proteins.
Primary human bronchial epithelial cells were allocated into four groups: (1) control group, (2) intermittent hypoxia group, (3) sustained hypoxia group, and (4) cigarette smoke exposure group. Apoptosis in each group was assessed by flow cytometric analysis. The expression levels of ZO-1, occludin, and claudin-1 were evaluated via Western blotting. Furthermore, trans-epithelial electrical resistance (TEER) was measured using an epithelial voltohmmeter to assess barrier function.
(1) Compared with the control group, the intermittent hypoxia group exhibited no significant differences in apoptosis rate, TEER, or the expression of tight junction proteins ZO-1, occludin, and claudin-1 (P > 0.05). In contrast, both the sustained hypoxia and cigarette smoke groups demonstrated significantly elevated apoptosis rates (P < 0.05). Claudin-1 expression was significantly reduced in the sustained hypoxia group (P < 0.05), while the increase in ZO-1 expression was not statistically significant (P > 0.05). In the cigarette smoke group, expression levels of ZO-1, occludin, and claudin-1 were all markedly decreased (P < 0.05). (2) Compared with the control group, TEER values were significantly reduced in both the sustained hypoxia and cigarette smoke groups (P < 0.05). (3) A significant difference in ZO-1 expression was observed between the sustained hypoxia and cigarette smoke groups (P < 0.05).
Hypoxia modulates the expression of tight junction proteins in human bronchial epithelial cells, disrupts intercellular junctional integrity, increases epithelial permeability, and ultimately impairs barrier function.
缺氧可损害细胞和器官功能，导致细胞凋亡及引发各种疾病。目前，关于肺缺氧的研究较多，但关于支气管损伤的研究较少。本研究旨在探讨缺氧对人支气管上皮细胞屏障功能及紧密连接蛋白表达水平的影响。
将原代人支气管上皮细胞分为四组：（1）对照组；（2）间歇性缺氧组；（3）持续性缺氧组；（4）香烟烟雾暴露组。采用流式细胞术分析每组细胞凋亡情况。通过蛋白质免疫印迹法评估紧密连接蛋白ZO-1、闭合蛋白和Claudin-1的表达水平。此外，使用上皮伏特计测量跨上皮电阻（TEER）以评估屏障功能。
（1）与对照组相比，间歇性缺氧组在细胞凋亡率、TEER以及紧密连接蛋白ZO-1、闭合蛋白和Claudin-1的表达方面均无显著差异（P＞0.05）。相反，持续性缺氧组和香烟烟雾组的细胞凋亡率均显著升高（P＜0.05）。持续性缺氧组Claudin-1表达显著降低（P＜0.05），而ZO-1表达的增加无统计学意义（P＞0.05）。在香烟烟雾组中，ZO-1、闭合蛋白和Claudin-1的表达水平均显著降低（P＜0.05）。（2）与对照组相比，持续性缺氧组和香烟烟雾组的TEER值均显著降低（P＜0.05）。（3）持续性缺氧组和香烟烟雾组之间ZO-1表达存在显著差异（P＜0.05）。
缺氧可调节人支气管上皮细胞中紧密连接蛋白的表达，破坏细胞间连接完整性，增加上皮通透性，最终损害屏障功能。
