关键词: 类风湿关节炎, 牛Ⅱ型胶原, Wistar大鼠, 模型, 评价

Abstract: Objective　To establish a rheumatoid arthritis (RA) model in Wistar rats using an adjuvant combined collagen tail injection method, and to evaluate the model through pharmacological intervention. Methods　Thirty male Wistar rats aged 6-8 weeks with an average body weight of (170±10) g were included in this study. Six rats were assigned to the normal control group, and the remaining 24 rats were used to establish RA models via immunization with bovine type II collagen (CII) combined with Freund’s adjuvant. Primary and booster immunizations were performed by multi-site intradermal injection of collagen-adjuvant emulsion at the base of the tail. Twenty days after the primary immunization, paw volume, paw thickness, arthritis index and body weight were measured to verify model establishment. A total of 18 rats with successful modeling were selected and randomly divided into three groups: model group, methotrexate (MTX) group and etanercept group (n=6). All animals were treated once every three days for 9 consecutive weeks. MTX was administered via intraperitoneal injection, while etanercept was given by subcutaneous injection. Rats in the normal control and model groups received an equal volume of 0.9% sodium chloride solution. During the intervention, the arthritis index and joint swelling were assessed every three weeks, and serum levels of tumor necrosis factor-α (TNF-α) and anti-CII antibodies were detected. Upon completion of intervention, the pathological conditions of ankle and knee joints in the hind limbs of rats were observed through imaging and histopathological testing, as well as the expression changes of interleukin-6 (IL-6), interleukin-17A(IL-17A), and vascular endothelial growth factor (VEGF) in synovial tissue. The therapeutic effects of the two drugs were comprehensively evaluated.Results　Compared with the normal group, the model group showed significantly increased paw thickness, paw volume and arthritis index in RA rats, as well as elevated expression of IL-6, IL-17A and VEGF in synovial tissues of the hind-limb ankle and knee joints (P<0.05, P<0.01). Severe destruction of articular cartilage and massive fibrous tissue hyperplasia were observed in the joint cavity. After intervention with MTX or etanercept, paw thickness, paw volume and arthritis index of RA rats were significantly reduced. Serum anti-CII antibody titers, TNF-α levels, and the expression of IL-6, IL 17A and VEGF in synovial tissues of the hind-limb ankle and knee joints were all significantly decreased (P<0.05, P<0.01). The severity of articular cartilage destruction was alleviated, fibrous tissue hyperplasia was reduced, and symptoms including joint space narrowing, joint ankylosis, inflammatory cell infiltration, erosion and destruction were improved.Conclusion　The RA model in Wistar rats induced by the modified adjuvant-combined collagen method recapitulates the pathological features of human RA and is suitable for efficacy studies of therapeutic drugs for RA.

Key words: rheumatoid arthritis, bovine type II collagen, Wistar rats, model, evaluation