An Experimental Study About The Influence Of Sinomenine On The JAK/STAT Signaling Pathway Induced By IL-35 In Collagen Induced Arthritis Mice

ObjectiveBased on the important role of JAK/STAT signaling pathway which mediated by IL-35 in rheumatoid arthritis,we explored the pathogenesis of rheumatoid arthritis and the effect of sinomenine,provide the basis for sinomenine for treatment of rheumatoid arthritis.Method30 healthy DBA/1 mice,male,6 weeks old,grade SPF,randomly divided into 4groups: blank control group,CIA model group(CIA group),methotrexate treatment group(MTX group),sinomenine treatment group(SIN group).Modeling them with type II collagen emulsion,28 days after the success of the model,Group SIN was given a solution of 0.1mg/ml containing SIN,2ml,once a day;Group MTX was given a solution of 0.1mg/ml containing MTX,2ml,once a week;The blank control group and the model group were given the physiological salt 2ml,once a day.Record and evaluate the AI scores of mice in each group after 21 days continuous gavage;then kill all mice and take material,observation of histopathological changes of synovium in mice by HE staining,determination of the concentration of IL-35,TNF-?,and IL-17 in the serum of experimental mice by ELISA,detection of protein expression of p-JAK1,p-STAT1 and p-STAT3 in synovial tissue by Western blot.Result1.d21 to d28,compared with the blank control group,the AI scores of all the other mice were significantly increased(P<0.05);d21 to d35,compared with the CIA group,there was no significant difference in AI scores between group SIN and MTX group(P>0.05);d35 to d49,compared with the CIA group,the AI scores of SIN group and MTX group decreased significantly(P<0.05),and there was not statistically significante between group SIN and MTX group(P>0.05).2.Compared with the blank control group,the synovitis cell infiltration andsynovial cells proliferated obviously in CIA group;compared with the CIA group,the synovitis cell infiltration and cell proliferation in group MTX and SIN mice were obviously reduced.3.Compared with the blank control group,the expression of TNF-? and IL-17 in group SIN and MTX decreased significantly(P<0.05);compared with the blank control group,the expression of IL-35 in the serum of CIA group was significantly decreased(P< 0.05);compared with the CIA group,the expression of IL-35 in group SIN and MTX were significantly increased(P<0.05).4.Compared with the blank control,the expression level of p-JAK1,p-STAT1 and p-STAT3 protein in the synovial tissue of group CIA were significantly increased(P<0.05);compared with the blank control,the expression level of p-JAK1,p-STAT1 and p-STAT3 protein in group SIN and MTX group were significantly decreased(P<0.05).ConclusionSinomenine can reduce arthritis in CIA mice,which may be related to promoting IL-35 expression and inhibiting JAK/STAT signaling pathway.