Song Hou-Pan, Li Xin, Yu Rong, Zeng Guang, Yuan Zhen-Yi, Wang Wei, Huang Hui-Yong, Cai Xiong
Hunan Provincial Key Laboratory of Diagnostics in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
Hunan Department of Education's Key Laboratory of Translational Chinese Medicine, Changsha, Hunan 410007, P.R. China.
Exp Ther Med. 2015 Oct;10(4):1483-1488. doi: 10.3892/etm.2015.2667. Epub 2015 Jul 31.
The aim of the present study was to determine a more specific, efficient and simple method for the induction of collagen-induced arthritis (CIA) in rats. Different strains of rats were injected at the base of the tail with bovine type II collagen (CII) emulsified in incomplete Freund's adjuvant (IFA). The onset and severity of arthritis were evaluated by clinical assessment. The established CIA model was analyzed using a comprehensive examination of clinical, hematological, histological and radiological parameters. The results demonstrated that Wistar rats were the most susceptible strain to CIA followed by Wistar Furth rats, with Sprague Dawley rats being the least susceptible. Following primary and booster immunization, female Wistar rats developed severe arthritis, with an incidence of >83% and low variability in clinical signs. The development of arthritis was accompanied by a significantly elevated erythrocyte sedimentation rate compared with that in the control rats. The radiographic examination revealed bone matrix resorption, considerable soft tissue swelling, periosteal new bone formation and bone erosion in the arthritic joints of the CIA rats. Histopathologically, the synovial joints of CIA rats were characterized by synovial hyperplasia, pannus formation, marked cellular infiltration, bone and cartilage erosion and narrowing of the joint space. The administration of an intradermal injection of only 200 µg bovine CII emulsified in IFA at the base of the tail therefore leads to the successful development of a CIA rat model. This well-characterized CIA rat model could be specifically used to study the pathophysiology of human rheumatoid arthritis as well as to test and develop anti-arthritic agents for humans.
本研究的目的是确定一种更特异、高效且简便的方法来诱导大鼠胶原诱导性关节炎(CIA)。将不同品系的大鼠在尾根部注射用不完全弗氏佐剂(IFA)乳化的牛II型胶原(CII)。通过临床评估来评价关节炎的发病情况和严重程度。使用临床、血液学、组织学和放射学参数的综合检查对建立的CIA模型进行分析。结果表明,Wistar大鼠是对CIA最敏感的品系,其次是Wistar Furth大鼠,而Sprague Dawley大鼠最不敏感。在初次免疫和加强免疫后,雌性Wistar大鼠发生严重关节炎,发病率>83%,临床症状的变异性低。与对照大鼠相比,关节炎的发展伴随着红细胞沉降率显著升高。放射学检查显示CIA大鼠关节炎关节处有骨基质吸收、明显的软组织肿胀、骨膜新骨形成和骨侵蚀。组织病理学上,CIA大鼠的滑膜关节表现为滑膜增生、血管翳形成、明显的细胞浸润、骨和软骨侵蚀以及关节间隙变窄。因此,仅在尾根部皮内注射200μg用IFA乳化的牛CII就能成功建立CIA大鼠模型。这种特征明确的CIA大鼠模型可专门用于研究人类类风湿关节炎的病理生理学,以及测试和开发用于人类的抗关节炎药物。