Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
Int J Mol Med. 2023 Aug;52(2). doi: 10.3892/ijmm.2023.5270. Epub 2023 Jun 23.
High‑altitude acute hypoxia is commonly associated with respiratory cardiovascular diseases. The inability to adapt to acute hypoxia may lead to cardiovascular dysfunction, lung injury and even death. Therefore, understanding the molecular basis of the adaptation to high‑altitude acute hypoxia may reveal novel therapeutic approaches with which to counteract the detrimental consequences of hypoxia. In the present study, a high‑altitude environment was simulated in a rat model in order to investigate the role of the high mobility group protein‑1 (HMGB1)/receptor for advanced glycation end products (RAGE)/NF‑κB and F2/Rho signaling pathways in lung injury induced by acute hypoxia. It was found that acute hypoxia caused inflammation through the HMGB1/RAGE/NF‑κB pathway and coagulation dysfunction through the F2/Rho pathway, both of which may be key processes in acute hypoxia‑induced lung injury. The present study provides new insight into the molecular basis of lung injury induced by acute hypoxia. The simultaneous activation of the HMGB1/RAGE/NF‑κB and F2/Rho signaling pathways plays a critical role in hypoxia‑induced inflammatory responses and coagulation abnormalities, and provides a theoretical basis for the development of potential therapeutic strategies.
高海拔急性缺氧通常与呼吸、心血管疾病相关。无法适应急性缺氧可能导致心血管功能障碍、肺部损伤，甚至死亡。因此，了解适应高海拔急性缺氧的分子基础可能揭示出对抗缺氧有害影响的新的治疗方法。在本研究中，通过大鼠模型模拟高海拔环境，旨在研究高迁移率族蛋白 B1（HMGB1）/晚期糖基化终产物受体（RAGE）/核因子-κB 和 F2/Rho 信号通路在急性缺氧诱导的肺损伤中的作用。结果发现，急性缺氧通过 HMGB1/RAGE/NF-κB 途径引起炎症，通过 F2/Rho 途径引起凝血功能障碍，这两者可能都是急性缺氧诱导肺损伤的关键过程。本研究为急性缺氧诱导的肺损伤的分子基础提供了新的见解。HMGB1/RAGE/NF-κB 和 F2/Rho 信号通路的同时激活在缺氧诱导的炎症反应和凝血异常中发挥着关键作用，为潜在治疗策略的开发提供了理论依据。
