Abstract: 【Objective】 The aim of this experiment was to explore the targets and mechanisms between the main drug components of total glucosides of paeony (TGP) and pulmonary interstitial fibrosis in rheumatoid arthritis (RA) through network pharmacology.【Method】 By searching multiple databases, according to two ADEM parameters of oral bioavailability (OB)＞30% and drug likeness (DL)＞0.18, the main active ingredients and gene targets of total glucosides of paeony were screened out.The gene targets of RA and pulmonary interstitial fibrosis were screened by searching DrugBank, GeneCards, OMIM, TTD, DisGenet and other databases.The gene names of target proteins were converted by UniProt database, and the targets of total glucosides of paeony in the treatment of RA and pulmonary fibrosis were collected.The intersection of ingredients and disease targets were obtained, Venn diagram was made.The target intersection was imported into the STRING database to draw the PPI network diagram, and the intersection was copied and pasted into the DAVID database for GO function and KEGG signaling pathway analysis, and the mechanism of its treatment of RA with pulmonary interstitial fibrosis was analyzed in depth. Wistar rats were divided into blank group, model group, total glycosides of peony group, and tofacitinib group. The lung index was measured to reflect the edema and inflammatory response of lung tissue, HE staining was used to observe the inflammatory response of lung tissue and ankle joint synovium in each group, and Masson staining was used to observe the collagen deposition in lung tissue.【Result】 A total of 85 components of total glucosides of paeony were screened by searching the TCMSP database.According to OB＞30% and DL＞0.18, 9 main components were screened.A total of 1 625 RA gene targets and 1 930 pulmonary interstitial fibrosis gene targets were screened from DrugBank, DisGenet, OMIM, TTD and GeneCards databases.A total of 65 terms of molecular functions, 37 terms of cell components, 350 terms of biological processes and 141 enrichment pathways were obtained by GO function and KEGG signaling pathway enrichment analysis.Through the Chinese medicine-target-pathway network diagram, TNF, IL6, AKT1, VEGFA, MMP9, JUN, PPARG, CASP3, PTGS2, and ICAM1 in the top 10 of Degree were used as the key targets for the treatment of RA pulmonary interstitial fibrosis.The results of animal experiments showed that compared with model group, the arthritis score and lung index of the treatment group decreased. HE staining revealed a decrease in the infiltration of inflammatory cells in the joint and lung tissues of the total glycosides of peony group. Masson staining found that total glycosides of peony ccould reduce fibrous lesions in the form of strips. It indicated that total glucosides of paeony could not only treat RA, but also delay collagen deposition and inflammation of pulmonary interstitial fibrosis.【Conclusion】 Total glucosides of paeony acted on multiple targets and pathways in inflammatory response, immunoregulation, cell differentiation and proliferation through various components, and delayed the development of pulmonary interstitial fibrosis in RA through the synergistic interaction between targets and pathways.

Key words: network pharmacology; total glucosides of paeony; rheumatoid arthritis; pulmonary interstitial fibrosis; mechanism