A Comparative Study Of Methotrexate,leflunomide,Cyclophosphamide And Between Two Combined In Collagen-Induced Arthritis Rats

BackgroundRheumatoid arthritis(RA) is a kind of autoimmune disease which can cause disability highly.70%of the patients have joint erosion, of whom about90%occured in the first2years. About14%of patients stop working in the fist12months. In recent10years, the biggest progress in RA field has been early diagnosis and early combination therapy, which is vital for reducing bone damage and relapse. Nowdays, the combined schemes are of various kinds and the effects are different. It is needed to explore effective and economy combined treatment for improving patients'conditions, reducing disability rates and improving the qulity of life.ObjectiveCompare the effects of methotrexate, leflunomide, cyclophosphamide and between two combined by observing the CIA rat symptom and the rates of synovial cell apoptosis. Obtain the best therapy scheme and provide theory basis for clinic work.Methods1. Adult SD rats received mixed liquor of cattle Ⅱ collagen and Freund's complete adjuvant (CFA) by multiple intradermal injection, and they received booster immunization by intraperitoneal injection after2weeks. Then CIA rats were made.2.70CIA rats were divided into7groups randomly, model control group, MTX group, LEF group, CTX group, MTX+LEF group, MTX+CTX group, LEF+CTX group, other10rats were normal control group. Test in vivo for9weeks and begin to give drugs after initial immunity3weeks.3. Assess the AI and measure joint swelling by slide calliper rule at different time points.4. At the9th week, observe X-ray changes, synovial pathological changes Of all groups, then test synovial cell apoptosis by TUNELResults1. Achievement ratio of model is91.3%(73/80):It was evaluated according to symptoms, X-ray changes and pathological changes of model rats. 2. Joint swelling and AI:At the9th weeks, the joint swelling of all treatment groups are lightened than CIA model group(P<0.05), combined treatment groups are lightened than single treatment (P<0.05), MTX+CTX group and LEF+CTX are lightened than MTX+LEF(P<0.05). The AI of all treatment groups are lightened than CIA model group(P<0.05), combined treatment groups are lightened than single treatment (P<0.05).3.Synovial cell apoptosis:At the9th weeks, the percent of apoptosis of all treatment groups are higher than CIA model group(P<0.05), combined treatment groups are higher than single treatment (P<0.05), MTX+CTX group and LEF+CTX are higher than MTX+LEF(P<0.05).4.MTX or LEF and CTX have interaction(P<0.05), MTX and LEF don not have interaction(P>0.05).Conclusions1.The effects of MTX, LEF, CTX between two combined are better than them used alone.2.MTX+CTX and LEF+CTX have better effects than MTX+LEF in relieving foot swelling degree and promoting apoptosis.3.MTX, LEF and CTX have synergic action, MTX and LEF don not have synergic action.