Mechanism of Yuxuebi Tablets in treating synovial inflammation in rheumatoid arthritis based on transcriptomics
This study investigated the mechanism of Yuxuebi Tablets(YXB)in the treatment of synovial inflammation in rheuma-toid arthritis(RA)based on transcriptomic analysis.Transcriptome sequencing technology was employed to analyze the gene expression profiles of joint tissues from normal rats,collagen-induced arthritis(CIA)rats(an RA model),and YXB-treated rats.Common diffe-rentially expressed genes(DEGs)were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.RA synovial inflammation-related target genes were retrieved from the OMIM and GeneCards databases.Venny 2.1 software was used to identify the intersection of YXB target genes and RA synovial inflammation-related target genes,and GO and KEGG enrichment analyses were performed on the intersecting target genes.Immunohistochemistry was used to assess the protein ex-pression levels of the inflammatory factors interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in rat joint tissues.Western blot analysis was employed to measure the expression levels of key proteins in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.A total of 2 058 DEGs were identified by intersecting the genes from the normal group vs model group and the model group vs YXB treatment group.A search in OMIM and GeneCards databases yielded 1 102 RA synovial inflammation-related target genes.After intersecting with the DEGs in the YXB treatment group,204 intersecting target genes were identified,primarily in-volving biological processes such as immune response,signal transduction,and inflammatory response;cellular components including plasma membrane,extracellular space,and extracellular region;molecular functions like protein binding,identical protein binding,and receptor binding.These target genes were mainly enriched in signaling pathways such as PI3K/Akt,cytokine-cytokine receptor in-teraction,and Janus kinase/signal transducer and activator of transcription(JAK/STAT).Western blot results showed that YXB at low,medium,and high doses could significantly inhibit the expression levels of key proteins in the PI3K/Akt signaling pathway in rat joint tissues in a dose-dependent manner.Immunohistochemistry further confirmed these findings,showing that YXB not only sup-pressed the protein expression levels of the inflammatory factors IL-1β and TNF-α in the joint synovial tissues of CIA rats,but also inhibi-ted p-Akt protein expression.In conclusion,this study used transcriptomic analysis to uncover the key mechanisms of YXB in inhibiting synovial inflammation and alleviating the progression of RA,with a focus on its role in suppressing the PI3K/Akt signaling pathway.
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