Liu Shi-Yan, Ruan Hang, Li Shu-Sheng
Department of Critical-Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, China.
Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Eur J Med Res. 2025 Aug 31;30(1):827. doi: 10.1186/s40001-025-03107-z.
Sepsis is a life-threatening condition marked by an abnormal host response to infection that can result in organ dysfunction, making it recognized as one of the primary causes of acute respiratory distress syndrome (ARDS). The pathophysiology of sepsis involves a cascade of events, including heightened pulmonary capillary permeability, dysfunction of alveolar epithelial cells, and the infiltration of inflammatory cells, such as neutrophils, macrophages, monocytes, and lymphocytes. The presence of these inflammatory cells triggers capillary leakages, alveolar epithelial damage, and the accumulation of fluid within the alveolar spaces, leading to compromised gas exchange, acute respiratory failure, and the progression to ARDS. In this complex scenario, Hypoxia-Inducible Factor-1α (HIF-1α) emerges as a pivotal player in maintaining cellular oxygen homeostasis and responding to hypoxia and inflammatory stimuli. This narrative review delves into the intricate molecular and biological characteristics of HIF-1α, elucidating its regulatory role within the context of sepsis and ARDS. By exploring the therapeutic potential of targeting HIF-1α, this review seeks to offer valuable insights into the underlying mechanisms linking sepsis to ARDS. Ultimately, this exploration of HIF-1α seeks to enhance our comprehension of sepsis pathogenesis, identify novel therapeutic avenues, and lay a strong theoretical groundwork for future clinical interventions.
脓毒症是一种危及生命的病症，其特征为宿主对感染的异常反应，可导致器官功能障碍，这使其被公认为是急性呼吸窘迫综合征（ARDS）的主要病因之一。脓毒症的病理生理学涉及一系列事件，包括肺毛细血管通透性增加、肺泡上皮细胞功能障碍以及炎症细胞（如中性粒细胞、巨噬细胞、单核细胞和淋巴细胞）的浸润。这些炎症细胞的存在引发毛细血管渗漏、肺泡上皮损伤以及肺泡腔内液体的积聚，导致气体交换受损、急性呼吸衰竭，并进展为ARDS。在这一复杂情形中，缺氧诱导因子-1α（HIF-1α）在维持细胞氧稳态以及对缺氧和炎症刺激作出反应方面成为关键因素。这篇叙述性综述深入探讨了HIF-1α复杂的分子和生物学特性，阐明了其在脓毒症和ARDS背景下的调节作用。通过探索靶向HIF-1α的治疗潜力，本综述旨在为脓毒症与ARDS之间的潜在机制提供有价值的见解。最终，对HIF-1α的这一探索旨在增进我们对脓毒症发病机制的理解，确定新的治疗途径，并为未来的临床干预奠定坚实的理论基础。
