Total glucosides of paeony improve complete freund's adjuvant-induced rheumatoid arthritis in rats by inhibiting toll-like receptor 2-mediated tumor necrosis factor receptor-associated factor 6/nuclear factor-kappa B pathway activation
摘要OBJECTIVE:To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony (TGP) based on toll-like receptor 2 (TLR2) mediated tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6)/nuclear factor-kappa B (NF-κB) pathway activation in rats with rheumatoid arthritis.METHODS:Adjuvant arthritis (AA) model was developed by complete freund's adjuvant (CFA) immunization.TGP (100,50,25 mg/kg) and celecoxib (2.8 mg/kg) were administered by intragastric administration for 21 d.Right hind paw swelling was assessed every 2 d.After 21 d,synovial changes of the ankle were detected by histopathology.CD4+ and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically.Gene and protein levels of toll-like receptor (TLR)2,TRAF6,tumor necrosis factor ligand superfamily member 6 (FASLG) in the spleen were assessed by RT-qPCR and Western Bolt,respectively.Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit.RESULTS:Paw swelling and synovium lesions were obviously aggravated in AA rats.These symptoms were significantly relieved by TGP.The ratio of CD4+/CD8+ T cell was increased in AA rats,while TGP reduced this increased ratio.Gene and protein levels of splenic TLR2,TFAR6 and FASLG,and nuclear NF-κB p65 in AA rats were significantly increased,but overtly inhibited by TGP.CONCLUSION:These findings suggest that TGP's anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.
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