[Animal modeling] - Comparison of pathological characteristics of collagen induced rheumatoid arthritis models in Wistar and Lewis rats

  Objective: To investigate the differences of symptoms and pathological characteristics between Wistar and Lewis rat models of rheumatoid arthritis (RA) induced by bovine type II collagen (CII)

  Methods: The first immunization was carried out by intradermal injection of mixed solution of CFA and bovine type 2 collagen (CII) at the tail root, and the immunization was strengthened by injection of mixed solution of Freund's complete adjuvant (IFA) at the 14th day. The RA models of Wistar and Lewis rats were established. The incidence of Wistar RA group and Lewis RA group was observed, the foot swelling and the serum anti CII antibody titer were measured, and the toe morphology and histopathology were examined at the 12th week, The expressions of VEGF, IL ⁃ 6, IL ⁃ 10 and IL ⁃ 17A in ankle synovium were measured

  Results: After collagen induction, Wistar and Lewis rats showed hind foot swelling on the 10th and 14th days, respectively, and reached the peak on the 21st and 24th days. The serum anti CII antibody titer increased significantly after the 3rd week (P<0.01), and the arthritis index (AI) increased significantly (P<0.01); The modeling rate of Wistar ⁃ RA group was 80%. At the fifth week, the foot swelling subsided and entered the gentle phase. The modeling rate of Lewis ⁃ RA group was 100%. At the seventh week, the foot swelling subsided and entered the gentle phase; At 12 weeks, severe cartilage erosion, synovial hyperplasia and inflammatory cell infiltration, angiogenesis and pannus formation of articular synovium, bone mineral density of femur and tibia of hind limbs were significantly decreased in both model groups (P<0.01), the expression of VEGF, IL 6, IL 17A in articular synovium was significantly increased (P<0.05, P<0.01), and the expression of IL 10 was significantly decreased (P<0.01). Compared with Wistar RA group, foot volume and foot palm thickness of Lewis RA group increased for a long time, AI was higher than Wistar RA group, synovial angiogenesis and pannus formation were more obvious, the expression of VEGF in ankle synovium was significantly higher than Wistar RA group (P<0.05), while the expression of IL 17A was significantly lower than Wistar RA group (P<0.05)

  Conclusion: Both Wistar ⁃ RA model and Lewis ⁃ RA model have symptoms of joint swelling, deformation, reduced activity, etc. The arthritis index increases, the expression of VEGF, IL ⁃ 6, IL ⁃ 17A in joint synovium increases, and the expression of IL ⁃ 10 decreases, which is consistent with clinical practice. However, the swelling duration of Wistar ⁃ RA model is short, while the swelling duration of Lewis ⁃ RA model is long, joint damage is more serious, angiogenesis and pannus formation are more obvious; Wistar ⁃ RA model has high expression of IL ⁃ 17A, while Lewis ⁃ RA model has high expression of VEGF, which may be related to its pathological characteristics