甲氨蝶呤、环磷酰胺对胶原诱导性关节炎大鼠血清TNF-α、IL-1的影响

摘要

Objective To study the effect of methotrexate ( MTX) and cyclophosphamide ( CTX) intermittent combination therapy on serum TNF-α and IL-1 levels in collagen-induced arthritis ( CIA) rats,in order to investigate the possible synergistic effect of the two drugs in the treatment of rheumatoid arthritis (RA). Methods A total of 90 Wistar rats were involved. Among them,75 received two times mixed liquor of cattle Ⅱ collagen and Freund′s com-plete adjuvant (CFA) by endermic injection to construct CIA rat model,and then divided into 5 groups randomly (15 rats in each group) and received MTX and CTX intermittent combination therapy or control drugs,respectively for 24 weeks. Another 15 non-CIA model rats were included as control group. The changes of arthritis index,arthritis swelling degree ,and appearance of imageology and pathology were observed;the serum levels of IL-1 and TNF-αwere detected by enzyme-linked immunosorbent assay. Results MTX in the doses of 0. 9 mg/kg and 2. 7 mg/kg a week could in-hibit the appearance of arthritis and serum levels of IL-1 and TNF-α in CIA rats. CTX in a dose of 24 mg/kg every 3 weeks had the same effects. Combination of MTX 0. 9 mg/kg a week and CTX 24 mg/kg every 3 weeks could inhibit arthritis index,arthritis swelling degree,and serum levels of IL-1 and TNF-α in CIA rats obviously,and the effect was better than single use of MTX or CTX. Conclusion MTX and CTX have synergistic effects at low dosage in the treat-ment of CIA.%目的：研究甲氨蝶呤( MTX)联合环磷酰胺( CTX)治疗对胶原诱导性关节炎( Collagen-induced arthritis,CIA)大鼠血清TNF-α、IL-1水平的影响,探讨甲氨蝶呤( MTX)联合环磷酰胺( CTX)治疗类风湿关节炎( Rheumatoid arthritis,RA)的机制。方法建立Ⅱ型胶原诱导的雌性Wistar大鼠CIA模型。取15只未造模的健康大鼠作为健康对照组( A组)。将造模成功的75只大鼠随机分成5组(每组15只),B组：造模对照组；C组：小剂量MTX组(每周0．9 mg/kg)；D组：大剂量MTX组(每周2．7 mg/kg)；E组：小剂量CTX组(每3周24 mg/kg)；F组：小剂量MTX联合小剂量CTX组( MTX每周0．9 mg/kg,CTX每3周24 mg/kg)。分别在6周、24周检测各组大鼠血清中TNF-α、IL-1的水平。结果联合应用MTX和CTX优于小剂量MTX、小剂量CTX单药治疗组。结论 MTX和CTX联合应用在RA的治疗中具有协同效应。