PDF(Pubmed)
Abstract：
Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α\'s mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. The review encompasses an analysis of the structural features, regulatory activation, and downstream signaling pathways of HIF-1α, alongside its mechanism of action in the pathophysiological processes of sepsis. Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications.
摘要：
脓毒症的特征是由感染引发的炎症反应失调引起的器官功能障碍。涉及多因素和复杂的分子机制。缺氧诱导因子-1α(HIF-1α),一个值得注意的转录因子，在脓毒症的发生和发展中起关键作用。本文旨在全面综述HIF-1α在脓毒症中的作用机制。仔细检查其参与炎症调节，低氧适应,免疫反应，和器官功能障碍。审查包括对结构特征的分析，监管激活，和HIF-1α的下游信号通路，其在脓毒症病理生理过程中的作用机制。此外，它将深入研究HIF-1α在调节炎症反应中的作用，包括它与炎症介质的关联，免疫细胞激活，和血管舒张。此外,将注意力集中在缺氧环境中HIF-1α的调节功能及其与细胞内信号的联系，氧化应激，和线粒体损伤。最后,将讨论HIF-1α作为靶向治疗的潜在治疗价值及其在脓毒症临床管理中的意义，旨在作为深入了解脓毒症发病机制和潜在治疗靶点的重要参考，为临床应用奠定理论基础。
