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目的初步探讨RANKL和M-CSF在CIA大鼠关节滑膜的表达及T-614、MTX的干预作用。方法通过鸡Ⅱ型胶原和完全弗氏佐剂混合的胶原乳剂免疫大鼠,建立CIA大鼠模型,将CIA大鼠随机分为模型对照组、T-614组、MTX组和T-614+MTX组。药物干预组大鼠分别用T-614、MTX及T-614联合MTX干预3周。关节炎指数(arthritis index,AI)评分评价关节炎程度,HE染色观察踝关节组织形态学变化,X线片观察骨侵蚀情况,高频超声观察踝关节并测量滑膜厚度,Western blot法检测滑膜RANKL和M-CSF表达。结果与正常对照组相比,模型对照组AI评分、病理评分、X线评分、超声下滑膜厚度、关节滑膜RANKL,M-CSF表达均增加(P<0.05);与模型对照组相比,T-614组、MTX组、T-614联合MTX组上述观察指标均降低(P<0.05);与T-614组、MTX组相比,T-614联合MTX组上述观察指标均降低(P<0.05);T-614组和MTX组之间上述观察指标差异无统计学意义(P>0.05)。结论 RANKL和M-CSF参与了CIA大鼠关节滑膜病变的发生、发展,T-614、MTX可能通过减少细胞因子RANKL,M-CSF的生成来延缓关节滑膜病变的进展,T-614与MTX具有一定的协同效应。
Objective To investigate the expression of RANKL and M-CSF in synovium of CIA rats and the intervention of T-614 and MTX. Methods CIA rat model was established by immunizing rats with collagen emulsion mixed with type Ⅱ collagen and complete Freund’s adjuvant. CIA rats were randomly divided into model control group, T-614 group, MTX group and T-614 + MTX group. The rats in the drug-intervention group were treated with T-614, MTX and T-614 respectively for 3 weeks. Arthritis index (AI) was used to evaluate the degree of arthritis. Histological changes of the ankle joint were observed by HE staining, bone erosion was observed by X-ray, synovial thickness was measured by high-frequency ultrasound, and synovial thickness was measured by Western blot Membrane RANKL and M-CSF expression. Results Compared with the normal control group, AI score, pathological score, X-ray score, synovial membrane thickness, RANKL and M-CSF expression in the synovium increased (P <0.05) Compared with T-614 group and MTX group, the above indexes in T-614 group, MTX group and T-614 combined MTX group were lower than those in T-614 group and MTX group (P < 0.05). There was no significant difference between the T-614 group and the MTX group (P> 0.05). Conclusions RANKL and M-CSF are involved in the occurrence and development of synovial lesions in CIA rats. T-614 and MTX may delay the progression of synovial lesions by decreasing the production of cytokines RANKL and M-CSF. T-614 and MTX has a synergistic effect.