痹祺胶囊对CIA大鼠OPG/RANKL表达的影响

The influence of Biqi capsule on the OPG/RANKL expressions in CIA rats

目的观察痹祺胶囊对类风湿关节炎CIA大鼠OPG/RANKL表达的影响,探讨其可能的骨保护机制。方法采用牛Ⅱ型胶原和完全弗氏佐剂复制类风湿关节炎CIA大鼠模型,设置空白组、模型组、甲氨蝶呤组、痹祺胶囊高中低剂量组,每组各12只。每周监测各组大鼠足趾容积和体质量变化;光镜下观察各组大鼠踝关节组织形态;RT-PCR法及Western blot法测定踝关节中OPG、RANKL的mRNA及蛋白表达;免疫组化法观察OPG、RANKL蛋白在踝关节中表达情况。结果模型组大鼠踝关节红肿明显,伴关节畸形,光镜下见关节滑膜及血管翳明显增生、关节破坏明显,各用药组均有改善,其中痹祺胶囊高剂量组改善最显著。模型组OPG mRNA及蛋白表达明显降低,各用药组OPG mRNA及蛋白表达显著升高(P<0.05),痹祺胶囊高剂量组升高最显著;模型组RANKL mRNA及其蛋白表达明显升高(P<0.05),各用药组RANKL mRNA及其蛋白表达显著降低(P<0.05),痹祺胶囊高剂量组降低最明显。结论痹祺胶囊能抑制CIA大鼠滑膜增生,减轻关节软骨及骨破坏,其机制可能与下调RANKL的表达,上调OPG表达,降低RANKL/OPG比值相关。

This study performed to observe the effects of the Biqi capsule on the expression of OPG/RANKL in CIA rats. The CIA rat model was induced by intradermal injection of complete freund＇ sadjuvant （CFA） and CII in SD female rats. Animals were randomly divided into the following six groups： normal, model, MTX, Biqi capsule high-dose group, middle-dose group and low-dose group, with 12 rats in each group. Quantitative real-time PCR, Western blot and immunohistochemistry were performed to analyze the mRNA and protein expression of OPG/ RANKL in the ankle joint; the histopathology of ankle joint was observed under light microscopy after twelve weeks treatment. The results revealed that the ankle joints of model rats demonstrated symptoms of severe swelling, erythema, synovium hyperplasia, pannus formation and cartilage damage, while MTX and Biqi treatment could alleviate these symptoms, especially Biqi high-dose. Comparison with normal group, the expressions of OPG mRNA and protein of model group were significant decreased, while MTX and Biqi capsule could reverse the decrease significantly （P 〈 0.05）; Comparison with normal group, the expression levels of RANKL mRNA and protein were significantly increased in model group, while MTX and Biqi capsule could reverse the increase significantly （P 〈 0.05）. In conclusion, Biqi capsule can obviously reduce the synovial hyperplasia, pannus formation and cartilage damage of the CIA rats, and the mechanism may relate to the increase of OPG expression and the decrease of RANKL expression.