摘要
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(M TX)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M TX联合小剂量CTX组(M TX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。
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 tw o drugs in the treatment of rheumatoid arthritis（ RA）. Methods A total of 90 Wistar rats w ere involved. Among them,75 received tw o times mixed liquor of cattle Ⅱ collagen and Freund＇ s complete 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 w eeks. Another 15 non-CIA model rats w ere included as control group. The changes of arthritis index,arthritis sw elling degree,and appearance of imageology and pathology w ere observed; the serum levels of IL-1 and TNF-α w ere detected by enzyme-linked immunosorbent assay. Results MTX in the doses of 0. 9 mg / kg and 2. 7 mg / kg a w eek could inhibit 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 3w eeks had the same effects. Combination of MTX 0. 9 mg / kg a w eek and CTX 24 mg / kg every 3 w eeks could inhibit arthritis index,arthritis sw elling degree,and serum levels of IL-1 and TNF-α in CIA rats obviously,and the effect w as better than single use of MTX or CTX. Conclusion MTX and CTX have synergistic effects at low dosage in the treatment of CIA.
出处
《实用药物与临床》
CAS
2015年第7期780-783,共4页
Practical Pharmacy and Clinical Remedies
基金
山西省自然科学基金(200711116)
关键词
胶原诱导性关节炎
甲氨蝶呤
环磷酰胺
协同效应
Collagen-induced arthritis
Methotrexate
Cyclophosphamide
Synergistic effect
