| 描述信息 |
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, cartilage erosion, bone destruction and pain, and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), a derivative of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. This study aims to investigate the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing (RNA-Seq), proteomics, and transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats, and significantly changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, and B cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating MMP2 and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings indicate that DHA holds promise as an anti-RA drug. |
