Effects Of BQC On The Expressions Of IL-6 And JAK/STAT Signalling Pathyway In CIA Rats

ObjectiveThis study performed to discuss the mechanisms of IL-6 and JAK/STAT signaling pathyway in RA and to explore the effects of the BQC on the expressions of the level of IL-6 and JAK/STAT signalling pathyway in rats with collagen-induced arthritis(CIA) and the possible mechanisms of BQC for treating RA.MethodThe model group was induced by intradermal injection of complete freund’s adjuvant(CFA) and bovine CII.The rats were randomly divided into six groups: normal group, model group, methotrexate group, high, middle and low doses of BQC groups, with 12 in each group. The changes of toes volume and weight were monitored weekly. After the treatment for twelve weeks, the serum level of IL-6 in rats was examined by ELISA, and the joint pathological morphology and the effects of BQC on the expressions of JAK3,STAT3 were evaluated by observing the pathological changes of ankle joint by light microscopy.Futhermore,the levels of JAK3,STAT3 in the ankle articular cartilage and synovial tissue were detected by Western blot and quantitative real-time PCR after the treatment for twelve weeks.Our results revealed that the rats of model group were severe swelling, erythema and the expressions of JAK3 and STAT3 were significantly increased(p<0.05) in the articular cartilage and synovial tissue compared with normal group,with joint deformity,reduction of movement and limp. The serum level of IL-6 was significantly increased in the model group rats compared with the normal group rats.The data of treated groups rats showed that a significant reduction in paw swelling compared to model group(p<0.05), especially BQC high-dose-treated rats(p<0.05). The serum level of IL-6 was significantly increased in the model group rats compared with the normal group rats,while the serum lelvel of IL-6 was significantly decreased in each treated group rats compared with the model group(P<0.05). The serum level of IL-6 in BQC high-dose treated group rats were significantly reduced compared with MTX group(P<0.05).however,there was no significantly difference in the serum level of IL-6 between BQC low-dose treated group rats and MTX treated group rats(P>0.05).Western blot and quantitative real-time PCR results displayed that the protein and mRNA levels of JAK3,STAT3 were increased significantly in the model group compared with normal group(P<0.05) and the expressions of JAK3 and STAT3 in treated groups could significantly reduce compared with model group(p<0.05),and high and middle doses of BQC groups were superior to methotrexate group(P<0.05),but there was no significant difference in BQC low dose group and MTX group(P>0.05).The histopathology of model ankle Result joints demonstrated that synovial hyperplasia,pannus formation and the obviously damage of cartilage Under light microscopy,while the surface of joint cartilage was smooth,with no synovial hyperplasia and pannus formation in the rats of normal group.And the synovial hyperplasia and cartilage damage of each treated group rats were observed significantly reduced,especially BQC high-dose group and methotrexate-treated group,which were superior to other treatment group rats.Conclusion(1)In Conclusion, the serum level of IL-6 and JAK3,STAT3 in articular cartilage and synovial tissue were significantly increased in the CIA model,which proved that the cytokines IL-6,JAK3,STAT3 play an important role in the pathogenesis and disease progression of RA.(2)BQC can obviously reduce the swelling degree,synovial hyperplasia,pannus formation and the damage of articular cartilage and bone in the CIA rats. Which mechanisms may be involved in inhibiting inflammatory cytokines IL-6 and regulating the expressions of JAK/STAT signalling pathyway such as JAK3 and STAT3.