Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Allied Health Professions, Queens, NY, USA.
J Immunotoxicol. 2010 Oct-Dec;7(4):239-54. doi: 10.3109/1547691X.2010.492254. Epub 2010 Jun 29.
Oxygen therapy using mechanical ventilation with hyperoxia is necessary to treat patients with respiratory failure and distress. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), causing cellular damage and multiple organ dysfunctions. As the lungs are directly exposed, hyperoxia can cause both acute and chronic inflammatory lung injury and compromise innate immunity. ROS may contribute to pulmonary oxygen toxicity by overwhelming redox homeostasis, altering signaling cascades that affect cell fate, ultimately leading to hyperoxia-induced acute lung injury (HALI). HALI is characterized by pronounced inflammatory responses with leukocyte infiltration, injury, and death of pulmonary cells, including epithelia, endothelia, and macrophages. Under hyperoxic conditions, ROS mediate both direct and indirect modulation of signaling molecules such as protein kinases, transcription factors, receptors, and pro- and anti-apoptotic factors. The focus of this review is to elaborate on hyperoxia-activated key sensing molecules and current understanding of their signaling mechanisms in HALI. A better understanding of the signaling pathways leading to HALI may provide valuable insights on its pathogenesis and may help in designing more effective therapeutic approaches.
氧疗使用机械通气加氧治疗呼吸衰竭和呼吸困难的患者是必要的。然而，长时间暴露于高氧环境会导致过多的活性氧（ROS）的产生，引起细胞损伤和多器官功能障碍。由于肺部直接暴露于高氧环境中，因此高氧可引起急性和慢性炎症性肺损伤，并损害固有免疫。ROS 通过破坏氧化还原平衡、改变影响细胞命运的信号级联反应，从而导致氧中毒性急性肺损伤（HALI），可能导致肺氧毒性。HALI 的特征是明显的炎症反应，伴有白细胞浸润、肺细胞（包括上皮细胞、内皮细胞和巨噬细胞）损伤和死亡。在高氧条件下，ROS 介导信号分子（如蛋白激酶、转录因子、受体和促凋亡和抗凋亡因子）的直接和间接调节。本综述的重点是阐述高氧激活的关键传感分子及其在 HALI 中的信号机制的最新认识。更好地了解导致 HALI 的信号通路可能有助于深入了解其发病机制，并有助于设计更有效的治疗方法。
