甲氨蝶呤联合环磷酰胺对胶原诱导性关节炎大鼠滑膜细胞p53表达的研究  

The effect of combined treatment of methotrexate and cyciophosphamide on synovial cell p53 expression incollagen-induced arthritis rats

作　　者：曲世晶[1] 李小峰[1] 王彩虹[1] 梁美娥[2] 

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001 [2]太原市第二人民医院风湿科

出　　处：《中华风湿病学杂志》2009年第1期42-44,共3页Chinese Journal of Rheumatology

基　　金：山西省自然科学基金（200711116）;山西省卫生厅科技攻关项目（200614）;山西医科大学第二医院青年科学基金（200601）

摘　　要：目的通过对类风湿关节炎（RA）动物模型胶原诱导性关节炎（CIA）大鼠的实验研究，从滑膜细胞p53表达的角度，探讨甲氨蝶呤（MTX）联合环磷酰胺（CTX）治疗RA协同作用和机制。方法建立Ⅱ型胶原诱导的雌性Wistar大鼠CIA模型，将造模成功的75只大鼠随机分成5组：CIA模型对照组、小剂量MTX治疗组（每周0．9mg／kg）、大剂量MTX治疗组（每周2．7mg／kg）、小剂量CTX治疗组（每3周24mg／kg）及小剂量MTX联合小剂量CTX组（MTX每周0．9mg／kg＋CTX每3周24mg／kg）。选8只大鼠为健康对照组，共6组。治疗24周后处死全部动物并取材，经固定、脱钙、包埋，通过免疫组织化学法检测滑膜细胞突变型p53的表达。结果突变型p53在CIA组表达上调（P〈0．05），联合治疗组下调突变型p53优于小剂量MTX、小剂量CTX组（P〈0．05），与大剂量MTX组相当（P〈0．05）。结论联合治疗组在下调突变型p53表达的作用均优于小剂量MTX、小剂量CTX单用药治疗组，提示MTX和CTX联合治疗为协同作用。Objective To investigate the effect of combination low-dose of methotrexate （MTX） and cyclophosphamide （CTX） intermittent therapy on the synovial cell p53 expression of collagen-indued arthritis Rats. The possible synergistic effect is examined and the possible mechaniams are evaluated. Methods Models of CIA were successfully established in 75 female Wistar rats. The CIA rats were then randomized into CIA mo-del group, low-dose MTX treatment group （0.9 mg·kg^-1·w^-1）, high-dose MTX treatment group （2.7mg·kg^-1·w^-1）, low-dose CTX treatment group （24 mg·kg^-1·w^-1）, low-dose MTX ＋ low-dose CTX treat-ment group （MTX 0.9 mg·kg^-1·w^-1, CTX 24 mg·kg^-1·w^-1）. Anther 8 non-CIA rats were included as normal controls. At the end of this 24-week study the synovium of ankle joints were obtained, fixed, decalcified, wrapped and cut into slices. The intensity of p53 mutations expressions was examined by immunohistochemistry method. Results The intensity of p53 mutations expression of synoviocytes in CIA model group was significantly higher than that in the controls. In addition, the p53 mutations expressions in the synoviocytes of the treatment groups were decreased markedly, which did not return to the baseline level. The improvement of p53 mutations in the combination treatment group was higher than the single treatment groups and the difference was statistically significant （P〈0.05）. However, the difference between the combination treatment group and high-dose MTX treatment group was not significant. Conclusion Low-dose of MTX combined with CTX has the same efficacy comparing to high-dose of MTX in inhibiting p53 expression of CIA rats synoviocytes, but it is superior to low-dose single drug group. The results suggest that the combination of MTX and CTX may be synergistic in the treatment of RA.

关 键 词：关节炎 实验性 甲氨蝶呤 环磷酰胺 细胞凋亡 P53 

分 类 号：R686[医药卫生—骨科学]