复方大黄散联用甲氨蝶呤对类风湿性关节炎大鼠血清RANKL及OPG的影响

Effects of the combination of compound rhubarb powder and methotrexate on the serum expression of RANKL and OPG in rheumatoid arthritis rats

目的探讨复方大黄散联用甲氨蝶呤(MTX)对类风湿关节炎(rheumatoid arthritis,RA)大鼠RANKL及OPG的影响。方法将48只SD雌性大鼠随机分为正常组、模型组、MTX组、联合组(复方大黄散+MTX),每组12只。除正常组外,其余各组用完全弗氏佐剂诱导大鼠RA模型。各组分别在致炎前、致炎后第1、2、4、6周跖围法测量大鼠足跖肿胀度。酶联免疫法检测血清致炎2周及治疗后6周RANKL及OPG的表达水平,光镜下观察各组大鼠踝关节的病理学改变。结果与模型组比较,各用药组在致炎2周后大鼠足跖肿胀度均开始明显下降(P<0.05);MTX组、联合组血清OPG的表达水平均升高,而RANKL水平均下降,且OPG与RANKL的比值升高(尤以联合组更明显),差异有统计学意义(P<0.05);光镜下,各用药组大鼠关节组织中炎症细胞浸润减少,血管翳生成减少,关节腔间隙增宽,关节软骨破坏减轻。结论复方大黄散联用甲氨蝶呤能更好地控制RA大鼠炎症,并可协同控制延缓大鼠骨破坏的发生,其作用机制可能通过升高OPG与RANKL的比例有关。

This study performed to explore the effects of the combination of compound rhubarb powder and methotrexate in rheumatoid arthritis（RA） by detecting the expression of RANKL and OPG in rheumatoid arthritis rats.Forty-eight female SD rats were grouped randomly into four groups： normal, control, methotrexate, combination of compound rhubarb powder with methotrexate, with 12 in each group. The RA model of SD rat was set up by intradermal injection of freund′s complete adjuvant（FCA）. The swelling degree of rat right rear foot was measured by plantar circumference; the expressions of RANKL and OPG in blood serum were detected by euzymelinked immunosorbent assay（ELISA）; while the morphology of ankle joint was observed under light microscopy. We found that in the treatment group, the swelling degree was began to decrease obviously（P0.05） from 2 weeks after modeling,while the expression of OPG in blood serum was increased, the expression of RANKL was decreased, and the ratio of OPG and RANKL was increased as compared with control. Results in this study demonstrate that the combination of compound rhubarb powder and methotrexate can not only control articular swelling, but also delay synergistically the occurrence of bone destruction. And the mechanism may involve in increasing the proportion of OPG and RANKL.