Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1β (IL-1β) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1β, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis.

吸入二氧化硅会导致职业病矽肺，其大多导致肺组织逐渐纤维化。先前的研究表明，缺氧诱导因子-1α（HIF-1α）和糖酵解相关基因在矽肺患者中表达上调。2-脱氧-D-葡萄糖（2-DG）作为硅肺小鼠模型中糖酵解抑制剂的作用及其分子机制仍不清楚。因此，我们使用2-DG观察其对矽肺小鼠模型肺部炎症和纤维化的影响。此外，还进行了体外细胞实验来探讨HIF-1α的具体机制。我们的研究发现，2-DG 下调了二氧化硅暴露诱导的肺泡巨噬细胞中的 HIF-1α 水平，并降低了肺部炎症中白细胞介素-1β (IL-1β) 的水平。此外，2-DG 还可减少二氧化硅诱导的肺纤维化。根据这些发现，我们假设 2-DG 通过抑制糖酵解来减少葡萄糖转运蛋白 1 (GLUT1) 的表达，从而抑制 HIF-1α 的表达，最终减少炎症细胞因子 IL-1β 的转录，从而减轻肺损伤。因此，我们阐明了HIF-1α在实验性矽肺模型中的重要调节作用以及2-DG的潜在防御机制。这些结果为2-DG治疗矽肺提供了可能的有效策略。