| ObjectiveThe purpose of this study to observe the experimental therapeutic effect and expressions of MMP-10 and IL-33 in rheumatoid arthritis (RA) rats of the compound rhubarb powder (CRP) for external application,and then to investigate the curative effect and potential mechanism of CRP on the treatment of RA.MethodSeventy-two SD rats were randomly divided into six groups:normal, model, voltaren, methotrexate, CRP, CRP with methotrexate, with 12 in each group. The AA model was induced by intradermal injection of complete freund’ sadjuvant (CFA) except normal group. Drugs were administered to each treatment group from the eighth day after modeling. The swelling degree of rear foot of rats were measured by plantar circumference, while the histopathology of ankle joint was observed under light microscopy after the treatment for six weeks. Western blot and quantitative real-time PCR were performed to analyzed the expressions of MMP-10 and IL-33 in the ankle joints.ResultOur results revealed that the right rear foot of the rats were severe swelling, erythema and the expressions of MMP-10 and IL-33 were significantly increased (p<0.05) in model group with activity decrease and limp; Treated groups performed significantly relieve in paw swelling compared to model group (p<0.05), especially CRP with methotrexate-treated rats(p<0.05). There were no significant difference among CRP-, voltaren-and methotrexate-treated rats (p>0.05). Western blot and quantitative real-time PCR results showed that there was a significant decrease on the expression of MMP-10 and IL-33 in treated groups compared with model group (p<0.05) after treated for six weeks.Under light microscopy, there were a large number of inflammatory cells and associated with plasma cells infiltrated, great quantities of pannus generated, articular cavity gap narrowed and different destruction levels of articular cartilage in the right ankle joints of model group, Ankle joints from each treatment group rats analyzed under light microscopy showed reductions of pannus response and inflammatory cells infiltration, the decrease of bone erosion and the widen of joint cavity gapt,especially CRP with methotrexate-treated rats.Conclusion(1)The levels of MMP-10 and IL-33 were significantly lower in the ankles of RA rat, and they were positively correlated. Which confirms that the pathogenesis of RA could affect the metabolism of articular cartigage and bone may through the MMP-10 by the degradation of extracellular matrix (ECM), while IL-33 destroys the balance of Thl/Th2 through mediating the immune response of Th2 cells, and IL-33 is also an important inflammatory agent in the development and happen of RA.(2) CRP can obviously decrease the acute inflammation of joints and improve the pathological morphology of cartilage and joint synovial tissusein RA Rats,which effect was comparable to voltaren and methotrexate.CRP can control early occurring of RA synovial inflammation and prevent bone destruction,while the mechanism may be involved in inhibiting the expressions of MMP-10 and IL-33. The ultimate goal of CRP was to eliminate joint swelling, reduce joint inflammation and Immune regulation and protect of the destruction of the articular cartilage and bone.(3) The effect of CRP combined with methotrexate was better than the other groups in eliminating joint swelling, reducing joint inflammation and reglulating the expressions of cytokines such as MMP-10 and IL-33.Which indicates that CRP with methotrexate is an effective externally drug for the treatment of rheumatoid arthritis. |
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