The effect of carfilzomib on rheumatoid arthritis in rats through inhibiting proliferation of FLS

Objective To observe the action of carfilzomib (CFZ) in adjuvant-induced arthritis (AIA) rat model, and explore the therapeutic effect and mechanism of carfilzomib on rheumatoid arthritis (RA). Methods Freund's adjuvants were used to induce arthritis in rats, and AIA models were successfully constructed. All rats were divided into seven groups:low-dose treatment group (1.0 mg/kg), middle-dose treatment group (1.5 mg/kg), high-dose treatment group (2.0 mg/kg), pre-treatment group (1.5 mg/kg), concurrent treatment group (1.5 mg/kg), AIA model control group and normal control group. The changes of hind feet of rats were observed and recorded. TRAP staining was used to analyses the inhabitation level of osteoclasts in different groups. ELISA was used to analyze the expression level of IL-1β, IL-6, TNF-α, and IFN-γ in peripheral blood. The CCK-8 assay was used to detect the proliferation activity of fibroblast-like synoviocytes. Results The observation on the changes of hind feet showed that the rats in all treatment group had the better joint condition than AIA model group. TRAP staining results showed that constrain of osteoclasts in the treatment group was much higher than the AIA model group. ELISA showed that level of IL-1β, IL-6, TNF-α, and IFN-γ in peripheral blood of all 5 treatment group were much lower those in AIA model group. CCK-8 results showed that low-dose, middle-dose and high-dose of carfilzomib had inhibited the proliferation activity of fibroblast-like synoviocytes significantly. Conclusion Carfilzomib is effective for the adjuvant-induced arthritis rats through suppressing the proliferation activity of fibroblast-like synoviocytes, down-regulation the expression of IL-1β, IL-6, TNF-α and IFN-γ to regulate inflammatory response, has a potential therapeutic value for RA.