中国中药杂志2025，Vol.50Issue(14)：3821-3834,14.DOI:10.19540/j.cnki.cjcmm.20250310.401
补阳还五汤靶向PPARG/SPP1/CD44信号通路:特发性肺纤维化中的脂质失调机制与治疗
Buyang Huanwu Decoction targets PPARG/SPP1/CD44 signaling pathway:mechanisms of lipid dysregulation and treatment in idiopathic pulmonary fibrosis
摘要
Abstract
Idiopathic pulmonary fibrosis(IPF)is a chronic progressive interstitial lung disease characterized by a complex pathogenesis and limited treatment options.Although studies have indicated that lipid metabolism dysregulation is associated with the progression of IPF,the core regulatory mechanisms remain unclear.By integrating RNA sequencing data from the GEO database,we identified four key genes related to lipid metabolism:peroxisome proliferator-activated receptor gamma(PPARG),secreted phosphoprotein 1(SPP1),caspase 3(CASP3),and platelet endothelial cell adhesion molecule 1(PECAM1).Further validation using single-cell RNA sequencing revealed the cell-specific expression patterns of these genes.The results found that PPARG was significantly downregulated in alveolar macrophages while SPP1 was significantly upregulated.Mechanistic studies indicated that PPARG negatively regulated SPP1 expression,and the interaction between SPP1 and cluster of differentiation 44(CD44)activated intercellular signaling pathways that promoted fibrosis.Through network pharmacology and molecular docking,it was predicted that the bioactive components of the traditional Chinese medicine formula,namely Buyang Huanwu Decoction may target PPARG to modulate lipid metabolism pathways.In a bleomycin-induced rat model with IPF,this paper randomly divided the rats into six groups(control,group,model group,pirfenidone group,and low,middle,and high-dose groups of Buyang Huanwu Decoction).The results demonstrated that Buyang Huanwu Decoction treatment significantly improved tissue pathological damage,reduced collagen deposition,and alleviated lipid metabolism dysregulation.Western blot analysis confirmed that Buyang Huanwu Decoction mediated the upregulation of PPARG and inhibited the activation of the SPP1/CD44 pathway.The multi-omics study elucidated the role of the PPARG/SPP1/CD44 pathway as a key regulatory factor in lipid metabolism in IPF,providing evidence that Buyang Huanwu Decoction exerted its antifibrotic effects through this novel mechanism and thus offering new insights into the therapeutic prospects for IPF.关键词
特发性肺纤维化/脂质代谢/肺泡巨噬细胞/补阳还五汤Key words
idiopathic pulmonary fibrosis/lipid metabolism/alveolar macrophages/Buyang Huanwu Decoction引用本文复制引用
李刚刚,潘晓川,王飞,杜全宇..补阳还五汤靶向PPARG/SPP1/CD44信号通路:特发性肺纤维化中的脂质失调机制与治疗[J].中国中药杂志,2025,50(14):3821-3834,14.基金项目
国家自然科学基金项目(82104829,82174347) （82104829,82174347）
