Wang Shu, Chen Hong, Li Zhi, Xu Guangxu, Bao Xiaochen
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Diving and Hyperbaric Medicine, Naval Medical Center, Shanghai, China.
Front Physiol. 2024 Oct 18;15:1474933. doi: 10.3389/fphys.2024.1474933. eCollection 2024.
Oxygen is an essential substance for the maintenance of human life. It is also widely used in clinical and diving medicine. Although oxygen is crucial for survival, too much oxygen can be harmful. Excessive oxygen inhalation in a short period of time can lead to injury, and the lung is one of the main target organs. Acute lung injury (ALI) induced by hyperbaric oxygen (HBO) is notably more severe than that caused by normobaric oxygen, yet systematic research on such injury and its regression is scarce. In this study, two independent experiments were designed. In the first experiment, mice were exposed to 2 atmospheres absolute (ATA), ≥95% oxygen for 2, 4, 6, and 8 h. Changes in lung histopathology, inflammation and expression of chemokines, alveolar-capillary barrier, and 8-OHdG were detected before and after the exposure. In the second experiment, these parameters were measured at 0 h, 12 h, and 24 h following 6 h of exposure to 2 ATA of ≥95% oxygen. Research indicates that ALI induced by HBO is characterized histologically by alveolar expansion, atelectasis, inflammatory cell infiltration, and hemorrhage. At 2 ATA, significant changes in the alveolar-capillary barrier were observed after more than 95% oxygen exposure for 4 h, as evidenced by increased Evans blue (EB) extravasation ( = 0.0200). After 6 h of HBO exposure, lung tissue pathology scores, 8-OHdG levels, and inflammatory and chemotactic factors (such as Il6, CCL2, CCL3, CXCL5, and CXCL10), intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1) were significantly elevated. Compared to lung injury caused by normobaric oxygen, the onset time of injury was significantly shortened. Additionally, it was observed that these markers continued to increase after leaving the HBO environment, peaking at 12 h and starting to recover at 24 h, indicating that the peak of inflammatory lung injury occurs within 12 h post-exposure, with recovery beginning at 24 h. This contradicts the common belief that lung injury is alleviated upon removal from a high-oxygen environment. However, EB levels, which reflect damage to the alveolar-capillary barrier, and VE-Cadherin (VE-Cad), tight junction protein 1 (ZO-1), ICAM1, and VCAM1 remained significantly altered 24 h after leaving the HBO environment. This suggests that the alveolar-capillary barrier is the most sensitive and slowest recovering part of the lung injury induced by HBO. These findings can provide insights into the pathogenesis and progression of lung injury caused by HBO and offer references for identifying corresponding intervention targets.
氧气是维持人类生命的必需物质。它在临床和潜水医学中也有广泛应用。尽管氧气对生存至关重要，但过量的氧气可能有害。短时间内过度吸氧会导致损伤，肺是主要的靶器官之一。高压氧（HBO）诱导的急性肺损伤（ALI）明显比常压氧引起的更严重，但关于这种损伤及其恢复的系统研究却很少。在本研究中，设计了两个独立实验。在第一个实验中，将小鼠暴露于2个绝对大气压（ATA）、≥95%氧气环境中2、4、6和8小时。在暴露前后检测肺组织病理学、炎症和趋化因子表达、肺泡-毛细血管屏障以及8-羟基脱氧鸟苷（8-OHdG）的变化。在第二个实验中，在暴露于2 ATA的≥95%氧气6小时后的0小时、12小时和24小时测量这些参数。研究表明，HBO诱导的ALI在组织学上的特征为肺泡扩张、肺不张、炎症细胞浸润和出血。在2 ATA时，暴露于95%以上氧气4小时后，观察到肺泡-毛细血管屏障有显著变化，伊文思蓝（EB）外渗增加（P = 0.0200）证明了这一点。HBO暴露6小时后，肺组织病理学评分、8-OHdG水平以及炎症和趋化因子（如白细胞介素6（Il6）、趋化因子配体2（CCL2）、趋化因子配体3（CCL3）、趋化因子XC亚族配体5（CXCL5）和趋化因子XC亚族配体10（CXCL10））、细胞间黏附分子1（ICAM1）和血管细胞黏附分子1（VCAM1）显著升高。与常压氧引起的肺损伤相比，损伤的发病时间明显缩短。此外，观察到这些标志物在离开HBO环境后继续升高，在12小时达到峰值并在24小时开始恢复，表明炎症性肺损伤的峰值出现在暴露后12小时内，恢复从24小时开始。这与从高氧环境中移出后肺损伤会减轻的普遍看法相矛盾。然而，反映肺泡-毛细血管屏障损伤的EB水平以及血管内皮钙黏蛋白（VE-Cad）、紧密连接蛋白1（ZO-1）、ICAM1和VCAM1在离开HBO环境24小时后仍有显著改变。这表明肺泡-毛细血管屏障是HBO诱导的肺损伤中最敏感且恢复最慢的部分。这些发现可以为HBO引起的肺损伤的发病机制和进展提供见解，并为确定相应的干预靶点提供参考。
