Non-coding RNA Transcriptomic Study Of Bi Zhong Xiao Decoction In Treating Rheumatoid Arthritis

Purpose: Rheumatoid arthritis(RA)is a chronic,progressive,systemic autoimmune disease whose pathogenesis is not fully understood.The clinical application and animal experiments of Bi Zhong Xiao Decoction(BZXD)have shown that it is effective in treating RA,but there is still a lack of systematic research on its pharmacodynamics and mechanism of action.In this subject,we aimed to explore the mechanism of efficacy of BZXD through transcriptomic analysis of lnc RNA and m RNA.Methods: The combination method of ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry(UPLC-MS/MS)was used to establish the quality control of BZXD,and to ensure the stability of BZXD during the whole experiment.The efficacy of BZXD in treating collagen-induced arthritis(CIA)was evaluated by body weight change,arthritis index score,paw swelling,serum inflammatory cytokine levels,pathomorphological staining,and Micro-CT.Arraystar rat lnc RNAm RNA chip was used to determine the lnc RNA and m RNA expression profiles of the Control,CIA and BZXD groups,and the differentially expressed lnc RNAs and m RNAs were screened.A lnc RNA-m RNA coexpression network was constructed for differentially expressed genes.Through GO function and KEGG pathway enrichment analysis,the biological functions and signaling pathways of differentially expressed genes were determined.Based on fold change and functional annotation,key differentially expressed lnc RNAs and m RNAs were selected for RTq PCR validation.Results: There was no significant difference in the content of each component in different batches of BZXD by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry,which can be used as the quality control for the experimental research of BZXD.The chemical components in BZXD include p-coumaric acid,ferulic acid,rosmarinic acid,ursolic acid,tanshinone IIA,salvianolic acid B,paeoniflorin,and glycyrrhizic acid.BZXD can effectively improve joint inflammation,and pathological damage and inhibit bone erosion in CIA rats.BZXD may improve bone erosion by regulating ECM-receptor interaction,MAPK signaling pathway,Focal adhesion,and Chemokine signaling pathway.In addition,this study identified lnc RNA uc.361-,ENSRNOT00000092834,ENSRNOT00000089244,ENSRNOT00000084631 and Acvr2 a m RNA may be potential targets of BZXD to inhibit bone erosion in RA.Conclusions: This study explored the pathogenic mechanism of bone erosion in CIA rats from the perspective of lnc RNA and m RNA and provided theoretical support for further elucidating the molecular mechanism of the efficacy of BZXD in treating RA.