甲氨蝶呤对类风湿关节炎骨破坏和修复的实验研究  

Experimental research of bone erosion and bone repiration about methotrexate in the treatment of rheumatoid arthritis

作　　者：董宏生[1] 胡荫奇[2] 于孟学[3] 王玉明[1] 李莉[1] 董占斌[1] 

机构地区：[1]首都医科大学附属北京中医医院风湿免疫科,100010 [2]中国中医科学院望京医院 [3]中国医学科学院北京协和医院风湿免疫科

出　　处：《北京医学》2007年第7期391-394,共4页Beijing Medical Journal

摘　　要：目的探讨甲氨蝶呤(MTX)对SD大鼠类风湿关节炎骨破坏、修复的作用机制和疗效。方法建立Ⅱ型胶原蛋白诱导的SD大鼠关节炎模型。将30只SD大鼠随机分为正常组、模型组和甲氨蝶呤治疗组(MTX组),每组10只。造模后10d,MTX组予0.1mg/100g的MTX灌胃,每周1次;模型组每日予生理盐水2ml/只灌胃。30d后,取双侧踝关节切片进行OPGmRNA和RANKLmRNA原位杂交实验。结果造模后,模型组和MTX组大鼠跖趾显著增厚(P﹤0.05),予MTX治疗后,MTX组大鼠跖趾厚度降低,与正常组比较无显著性差异;MTX组OPG平均吸光度为0.266±0.010,OPG阳性细胞数为(24.80±8.72)个,与模型组比较有显著性差异(P﹤0.05);模型组和MTX组RANKL平均吸光度和阳性细胞数与正常组比较均显著增加(P﹤0.05),但两组间无显著性差异。结论MTX通过上调OPG的表达,可提高OPG/RANKL的比例,从而竞争性抑制RANK和RANKL的结合,最终抑制破骨细胞的生成和活化,延缓关节周围骨的破坏。Objective To explore the mechanisms of bone erosion and effect of medications by analyzing the pathological change of bone erosion of joint and change of RANKL, OPG by in situ hybridization after methotrexate （MTX） treatment. Methods Collagen induced arthritis （CIA） animal models were developed. 30 female SD mice were diveded randomly into 3 groups （normal control, model group, and MTX group） with 10 in each group. （1） Model group：NS 2 ml was given every day; （2） Normal control：treated with nothing; （3） MTX group：MTX 0.1 mg/100 g B.W was given every week. At the end of the experiment both ankle joints were cut for pathological examination. OPG and RANKL was detected by in situ hybridization. Results The OPG of MTX group was higher than that of the model group, the difference was significant. OPG could competitively bind to RANKL and retarded the joint damage by inhibiting combination of RANKL with RANK. Conclusions MTX could increase the ratio of OPG/RANKL to inhibit the activation of osteoclasts, therefore it could decrease cartilage damage.

关 键 词：类风湿关节炎 甲氨蝶呤 骨破坏 骨修复 

分 类 号：R593.22[医药卫生—内科学]