以糖酵解为核心的糖代谢重编程在尘肺病发生发展与靶向治疗中的研究进展OA

Pneumoconiosis is a chronic interstitial lung disease caused by occupational exposure to mineral dust,characterized by persistent inflammation and progressive pulmonary fibrosis.Ef-fective therapeutic options,however,remain limited.Recent multi-omics studies have revealed that glucose metabolic reprogramming,particularly the abnormal activation of glycolysis,plays a critical role in the pathogenesis of fibrotic diseases.This review summarized the key components involved in glycolytic reprogramming,including rate-limiting enzymes such as hexokinase,phos-phofructokinase,pyruvate kinase,and lactate dehydrogenase,as well as regulatory factors such as hypoxia-inducible factor-1α(HIF-1α)and AMP-activated protein kinase(AMPK).Their roles in metabolic regulation and fibrogenesis were elaborated.Special emphasis was placed on alveolar macrophages and fibroblasts,in which enhanced glycolysis and lactate accumulation drive in-flammatory responses and collagen deposition,contributing to disease progression.Advances on pharmacological agents such as nintedanib,2-deoxyglucose,quercetin,metformin,and resveratrol were reviewed,highlighting their antifibrotic potential through modulation of gly-colytic enzymes or related signaling pathways.Additionally,the interactions between glycolysis and fatty acid metabolism,amino acid metabolism,and oxidative phosphorylation were dis-cussed,underscoring the significance of multi-pathway coupling in pneumoconiosis.Metabolic abnormalities in pneumoconiosis result from multi-level interactions across cells,molecules,and tissues.Consequently,future therapeutic strategies should shift from single-target interventions toward coordinated regulation of multiple pathways,integrating tissue-targeted drug delivery,metabolism-based stratified interventions,and multi-target combination therapies to achieve precision and personalized treatment.