| BackgroundRheumatoid arthritis(RA) is a mutilation autoimmune disease. Cytokines play important effects in enlarging immunologic derangement and joint destruction .IL-1 and TNF-αare critical cytokines , which cause symmetrical and invasive arthritis ,even joint dysfunction. Its distinctive pathologyical change is synovitis,which shows invasive hyperplasia of synovial tissue. Vegetation and pathology of synovium are similar to tumor in many ways. So it is important to inhibit synovial tissue hyperplasia and induce its apoptosis in treating RA.ObjectiveComparison of effects of low dose,large dose hydroxycamptothecin(HCPT) and methotrexate (MTX) therapy on collagen-induced arthritis rats by observing the symptoms,the level of serum IL-1 and TNF-αand the percentage of apoptosis of synovium with TUNEL colored is helpful to study which is the optimum therapy and is significant to explore potential value of HCPT in treatment of RA so that scientifical evidence can be provided to further study.Methods1. Adult Wistar rats received mixed liquor of cattleⅡcollagen and Freund's complete adjuvant (CFA)by multiple intradermal injection, and they received booster immunization by intraperitoneal injection intermitently three weeks . Then CIA rats were made.2. 32 CIA rats were divided into 5 groups randomly, A group(blank control group),B group(model control group),C group(MTX 2.0mg/kg/w),D group(HCPT 0.8mg/kg/w),E group(HCPT 2.0mg/kg/w).3. To detect the serum IL-1,TNF-αlevel by enzyme-linked immunosorbentassay at different time.4. Synovium of knee joint in hind limb of 15-week rats was colored with TUNEL apoptosis method, and then comparison of percent of apoptosis of synovial cell of each group was done by counting.5. To observe pathological changes of ankle joint at different time and to evaluate them by pathological integral.6. The results were analysed by the statistical software SPSS11.5.Results1. Achievement ratio of model : It was evaluated according to symptoms (including gross view,arthritis index,joint swelling degree)and pathological changes of model rats. 50 rats who had received mixed liquor of cattleⅡcollagen and CFA,but 32 developed symmetric polyarthritis, so achievement ratio of model is 64%.2. Evaluation of joint swelling degree:Red swelling of the joint was progressing after the first immunization with AI and swelling degree of foot reaching the peak about 40 days. The swelling gradually disappeared and came to chronic platflom time ,which could lead to joint rigidity,deformity,dysfuction and difficult in walking. AI and swelling degree of foot in B,C,D,E group is even higher than A group(P<0.05),but it is lower in C group than B group(P<0.05), while there is no statistical significance among C,D and E group(P>0.05) within 15 weeks.3. Level of serum IL-1,TNF-α:Compare to normal rats,the increase level of TNF-αand IL-1 reached the peak about 40 days and then decreased gradually.4. Count results of apoptosis cell with TUNEL staining in 15 weeks:The percent of apoptosis in B,C,D,E group is even higher than A group(P<0.05),and it is higher in C,D,E group than B group(P<0.05), while there is no statistical significance among C,D and E group(P>0.05). The effects in each treatment group were correspond.5. There was a positive linear correlation between serum TNF-α,IL-1 and swelling degree of foot.Conclusions1. Compare to MTX, HCPT has equal effects in decreaseing the level of serum IL-1,TNF-αof CIA rats, relieving foot swelling degree and promoting apoptosis.2. HCPT have potential value in the treatment of RA.
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