摘要
目的:明确佐剂中卡介苗含量对成功建立C57BL/6小鼠胶原性关节炎(Collagen in-duced arthritis,CIA)模型的影响,为开展类风湿关节炎(RA)的有关动物实验研究提供参考。方法:四个模型组以鸡Ⅱ型胶原(TypeⅡcollagen,CⅡ)与含不同浓度高毒卡介苗的完全弗氏佐剂(Completed Freund’s adjuvant,CFA)免疫C57BL/6小鼠诱导CIA,以关节炎指数为评价造模成功率,并对免疫成功模型进行一般状态观察、关节炎指数评分、脾脏指数计算、组织病理学和关节影像学检查。另设正常对照组。结果:四模型组小鼠踝关节分别于加强免疫后d4、d3、d3、d2天开始出现红肿,d14肿胀厚度达到高峰,小鼠死亡率分别为0%、5%、6%、80%,小鼠的CIA发生率分别为15%、60%、55%、死亡率高无数据;关节炎指数、脾脏指数均显著高于正常对照组(P<0.01);病理学结果显示:造模成功小鼠患病关节表现出周围炎性细胞浸润、滑膜增生、软骨和骨骼破坏等较为典型的变化;足爪X线摄片显示:关节间隙变窄,关节面不光滑,周围软组织影增厚;关节强直、畸形;正常对照组小鼠则无上述表现。结论:含2.5 mg/ml高毒卡介苗的完全弗氏佐剂,与鸡Ⅱ型胶原充分乳化,可成功诱导C57BL/6小鼠关节炎模型,免疫模型在临床发病特点、组织病理学改变等方面,较充分模拟了人类RA的病变特征,可适用于开展RA防治药物或其机制的实验研究模型。
Objective:To determine the impact of the content of BCG in adjuvant on collagen-induced arthritis model-establish- ment of C57BL/6 mice, and provide a reference for experimental-animal studies on rheumatoid arthritis. Methods: Four model groups with type II collagen and complete Freund's adjuvant containing different concentrations of highly toxic BCG C57BL/6 mice induced CIA, arthritis index was used to evaluate the success rate of modeling . The immune status of the successful model was monitored by general observation, arthritis index score, spleen index, histopathology and joint imaging observation. Reference group was for compar- ison. Results: The mice ankles of four model groups began to appear swelling after strengthen immunization day of d4, d3, d3, d2, (114. The swelling thickness reached maximum on d14. Mice mortality was 0% , 5% , 6% , 80% , CIA incidence were 15% , 60% , 55% , and high mortality was not recorded. The arthritis index and the spleen index were significantly higher than the reference group (P 〈 0.01 ). The pathology analysis indicated that the diseased joints of successful modeled mice exhibited inflammatory cell infiltra- tion for the surrounding inflammatory cells, synovial hyperplasia, cartilage and bone destruction. The paw X-ray showed joint space narrowing, less smoothing of articular surface, soft tissue shadow increased thick, joint stiffness , deformity. The mice of reference group exhibited no above performance. Conclusion: The complete Freund's adjuvant containing 2.5 mg/ml highly toxic BCG, emulsi- fied with chicken type 11 collagen, can successfully induce arthritis model of C57BL/6 mouse. These immune models well simulate lesion characteristics of human RA with aspects of clinical characteristics of disease, histopathology etc. The models are also applicable on conducting experimental research model of prevention and cure drug or mechanism for RA.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2014年第3期378-382,共5页
Chinese Journal of Immunology
基金
国家自然科学基金项目(81273986)
河北省青年基金项目(Q2012038)