脂肪酸代谢重编程作为肺纤维化干预新靶点的研究进展OA

Pulmonary fibrosis(PF)is a chronic progressive in-terstitial lung disease,which is mainly characterized by the de-struction of alveolar structure and excessive deposition of extra-cellular matrix.Currently,it lacks effective treatment options.Recent studies have indicated that fatty acid metabolism repro-gramming plays an important role in the pathogenesis and pro-gression of PF.This article systematically reviews the research progress of fatty acid metabolic reprogramming in PF from the abnormal regulatory mechanisms of fatty acid uptake,synthesis and oxidation.In terms of uptake,dysregulated expression of transport proteins such as CD36 and FABPs leads to intracellu-lar lipid accumulation and subsequent cellular injury.Regard-ing synthesis,FASN orchestrates the fibrotic progression via sig-naling pathways including Wnt/β-catenin.In oxidative metabo-lism,functional impairments of key molecules like CPT1A,AMPK,and PPARα result in disrupted fatty acid oxidation,which in turn induces mitochondrial dysfunction and activates profibrotic signaling.On this basis,this review further summa-rizes the intervention strategies targeting fatty acid metabolism,including dietary regulation,drug targets(such as FAAH,GPR84,PCSK9,and miR-33),natural products and Chinese herbal compound prescriptions,and specific fatty acid interven-tions,as well as other multi-modal therapeutic approaches,pro-viding new perspectives for restoring lipid metabolic balance and anti-fibrotic therapy.