Imaizumi K, Hinoue H, Ueno M, Takata I, Sato T, Minato Y, Takeshita M, Okaniwa A
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka-shi, Japan.
Jikken Dobutsu. 1990 Jan;39(1):27-34. doi: 10.1538/expanim1978.39.1_27.
Eight male DBA/1J mice immunized twice by intradermal injection of type II collagen were autopsied 12 weeks after the first immunization and analyzed for anti-type II collagen antibody level, and the limb joints were examined radiologically and histopathologically. Clinical onset of swelling and erythema in the limb joints occurred about 5 weeks after the first immunization and deformity of the limbs was observed in a few animals about 5 weeks later. Although there were marked individual differences, serum anti-type II collagen antibody levels were elevated in all animals. Histopathologically, the changes were similar to those seen in human rheumatoid arthritis and were characterized by proliferation of synovial lining cells, formation of granulation tissue with destruction of cartilage and subchondral bone, and ankylosis. Systematic examination of various joints of the fore- and hind-limbs revealed definitely that the sequence of arthritic lesions was not uniform. The knee joint was involved most frequently, but smaller joints such as the phalangeal joints were involved less frequently but exhibited severe changes. The significance of histopathological examinations in the evaluation of effects of anti-rheumatic drugs was discussed with reference to this model.
八只雄性DBA/1J小鼠通过皮内注射II型胶原蛋白进行了两次免疫,在首次免疫后12周进行解剖,分析抗II型胶原蛋白抗体水平,并对肢体关节进行放射学和组织病理学检查。肢体关节肿胀和红斑的临床发作在首次免疫后约5周出现,约5周后在少数动物中观察到肢体畸形。尽管存在明显的个体差异,但所有动物的血清抗II型胶原蛋白抗体水平均升高。组织病理学上,这些变化与人类类风湿性关节炎相似,其特征为滑膜衬里细胞增殖、形成肉芽组织并伴有软骨和软骨下骨破坏以及关节强直。对前肢和后肢的各个关节进行系统检查明确显示,关节炎病变的顺序并不一致。膝关节受累最为频繁,但诸如指关节等较小的关节受累较少,但变化较为严重。参照该模型讨论了组织病理学检查在评估抗风湿药物疗效中的意义。