摘要Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treating COPD,but the underlying mechanism is still unclear.Methods:This study explored the pathological mechanism of COPD through RNA-Seq analysis and single-cell sequencing data analysis.And the mechanism of ZBM and blood entering sRNAs for COPD was verified with network pharmacology analysis and in vitro experiments.Results:The results showed that inflammation and oxidative stress exacerbated the progression of COPD,and the expression of HSP90AA1,PTGS2,and AGRN genes significantly increased in the lung tissue of patients.Network pharmacology analysis suggests that the natural products contained in ZBM may directly target HSP90AA1,PTGS2,and AGRN for the treatment of COPD.Analysis of the blood entering sRNA contained in the decoction of ZBM revealed its excellent antioxidant and anti-macrophage polarization effects.Meanwhile,ZBM decoction,sRNA2,and sRNA5 reduce oxidative stress and inflammation by acting on prostaglandin-endoperoxide synthase 2(PTGS2),nitric oxide synthase 2(NOS2),ATP-binding cassette,subfamily C member 1(ABCC1),and xeroderma pigmentosum complementation group C(XPC)genes.Conclusion:Our study demonstrated that ZBM extract and ZBM derived sRNA2 and sRNA5 can relieve COPD by regulating PTGS2-NOS2-XPC-ABCC1 axis.