Dexmedetomidine Inhibits The Invasion,Migration,and Inflammation Of Rheumatoid Arthritis Fibroblast-like Synoviocytes By Reducing The Expression Of NLRC5

Background: Rheumatoid arthritis(RA)is a chronic,systemic,inflammatory,autoimmune dysfunction disease,and the joint synovial is the main target tissue.The typical pathological changes are abnormal hyperplasia of synovium and destruction of articular cartilage,which can lead to joint deformities.RA causes severe damage to the patient's body and psychology,and its etiology is unknown.The incidence of domestic adults is about 0.34%,and the number of female patients is higher than that of men.Current research suggests that fibroblast-like synoviocytes plays very important role in the inflammatory response and joint damage of rheumatoid arthritis.Dexmedetomidine(DEX)is a commonly used sedative in the clinic and can also be used as an aid in general anesthesia.Many studies have shown that dexmedetomidine has an anti-inflammatory effect in sepsis,and has an analgesic effect in monoarthritis.In this experiment,complete Freund's adjuvant were injected on the toes of rats to simulates rheumatoid arthritis model,fibroblast-like synoviocytes were extracted from rheumatoid arthritis patients and TNF-? was used to stimulate the cells,to explore the protective effect of dexmedetomidine on rheumatoid arthritis rat models and fibroblast-like synoviocytes.Methods: The animals were randomly divided into 8 groups,7 in each group,which were control group,model group,DEX(5?g/Kg,10?g/Kg,20?g/Kg)treatment group,DEX(5?g/Kg,10?g/Kg,20?g/Kg)and complete Freund's adjuvant(CFA)treatment group.Pathological score,arthritis score,paw swelling volume,the levels of IL-1?,IL-6,IL-17 A,and TNF-?,matrix metalloproteinases(MMP-3,MMP-9),the expression of NLRC5 were detected.In the cell experiment,human rheumatoid arthritis fibroblast-like synoviocytes were pretreated with dexmedetomidine(62.5n M,125 n M,250 n M)for 1 hour,and then the cells were stimulated with TNF-?(10ng / ml).Intracellular levels of IL-6,IL-1?,MMP-3,MMP-9,NLRC5 were measured by RT-q PCR and western blot,NLRC5 was silenced in the cells,and the levels of IL-6,IL-1?,MMP-3,and MMP-9 were measured again.Results: In adjuvant-induced arthritis(AA)rat models,it was found that Dexmedetomidine(DEX)(10 ?g/Kg,20 ?g/Kg)reduced pathological score,arthritis score,and paw swelling volume,and the levels of IL-1?,IL-6,IL-17 A,and TNF-? in serum.Moreover,by using WB and RT-q PCR,it was demonstrated that DEX can inhibit the expression of IL-1?,IL-6,MMP-3,MMP-9 in the synovial tissue of AA rats.In human rheumatoid arthritis fibroblast-like synoviocytes(RA-FLSs),DEX(250 n M,500 n M)was found to inhibit the expression of IL-1?,IL-6,MMP-3,MMP-9,stimulated with TNF-?.What is more,DEX can inhibit the invasion and migration of RA-FLSs stimulated by TNF-?.Finally,the expression of NLRC5 in RA-FLSs and AA rat models were also reduced by DEX.After silencing NLRC5 in RA-FLSs,the expression of IL-1?,IL-6,MMP-3,MMP-9,as well as the invasion and migration of cells,were significant reduced.Conclusion: These results indicate that dexmedetomidine can protect AA rat models and rheumatoid arthritis fibroblast-like synoviocytes by reducing NLRC5 expression.