类风湿关节炎SD大鼠模型的对比研究OA
Comparative investigation of a rheumatoid arthritis model in SD rats
目的 探讨胶原诱导性关节炎(CIA)与佐剂诱导性关节炎(AIA)SD大鼠模型中不同免疫注射部位(尾根部皮下与后足足跖部皮下)及溶剂(0.9％氯化钠溶液与3.6％乙酸溶剂)对模型稳定性、炎症反应及病理进程的影响,优化CIA大鼠模型的构建方法.方法 将120只雌性SD大鼠随机分为10组,包括空白组、AIA组及8种不同CIA建模方案(区分免疫部位与溶剂).动态观察各组大鼠在致敏后第7、14、21、28、35天的关节炎指数(AI)、血清抗环瓜氨酸肽抗体(anti-CCP)与类风湿因子(RF)抗体水平、踝关节组织病理变化以及IL-6、IL-17的蛋白与mRNA表达情况.结果 HAc-足足组(3.6％乙酸溶剂+双次后足足跖注射)在AI评分、血清anti-CCP与RF抗体水平及关节局部IL-6、IL-17表达方面均显著高于其他CIA组(P＜0.01),且上述指标在整个实验周期内保持高位稳定,踝关节苏木素-伊红(HE)染色显示其病理进程呈现典型的慢性、进行性特征,在模拟人类风湿关节炎(RA)方面明显优于传统AIA模型.传统AIA模型虽早期反应强烈,但第35天时病理显著缓解,呈现自限性.NS-足足组能诱导持续病理改变,但后期炎症强度有所回落.HAc-尾足组系统免疫应答强,但关节局部病理波动大,稳定性差.结论 HAc-足足方法所建立的动物模型,相较传统的AIA模型及HAc-尾足模型,表现出明显且稳定的类风湿关节炎慢性、进行性症状及病理特征,同时伴有高水平的IL-6、IL-17和anti-CCP、RF抗体,可能是一种较好的RA SD大鼠模型.
Objective This study aimed to investigate the effects of different immunization sites(subcutaneous tail base versus subcutaneous plantar hind paw)and solvents(0.9％sodium chloride solution and 3.6％acetic acid)on model stability,inflammatory response,and pathological progression in SD rat models of collagen-induced arthritis(CIA)and adjuvant-induced arthritis(AIA),and to optimize the methodology for constructing the CIA rat model.Methods Methods One hundred and twenty female SD rats were randomly divided into 10 groups,including a blank group,an AIA group,and eight groups subjected to different CIA modeling protocols(distinguishing immunization site and solvent).Dynamic observation of arthritis index(AI),serum anti-cyclic citrullinated peptide(anti-CCP)and rheumatoid factor(RF)antibody levels,histopathological changes of the ankle joint,and protein and mRNA expression of IL-6 and IL-17 were carried out on days 7,14,21,28,and 35 after sensitization.Results The HAc-Hind Paw-Hind Paw group(3.6％acetic acid solvent+double subcutaneous plantar hind paw immunization)showed significantly higher arthritis index(AI)scores,serum anti-CCP and RF antibody levels,and local joint IL-6 and IL-17 expression compared with other CIA groups(P＜0.01);these indicators remained at a high and stable level throughout the entire experimental period.Hematoxylin-eosin(HE)staining of the ankle joint revealed a typical chronic and progressive pathological process,and this group was significantly superior to the traditional AIA model in mimicking human RA.Although the traditional AIA model elicited a strong early response,it showed significant pathological remission by day 35,exhibiting a self-limiting nature.The NS-Hind Paw-Hind Paw group induced persistent pathological changes,but the intensity of inflammation declined in the later stages.The HAc-Tail-Hind Paw group generated a strong systemic immune response,but the local joint pathology fluctuated greatly and exhibited poor stability.Conclusion The animal model established by the HAc-Hind-Paw-Hind Paw method exhibited pronounced and stable chronic,progressive rheumatoid arthritis symptoms and pathological features compared with the traditional AIA model and the HAc-Tail-Hind Paw model,accompanied by high levels of IL-6,IL-17,anti-CCP antibodies,and RF antibodies,and may represent an improved SD rat model of RA.
吴华华;陈跃平;黄川洪
广西中医药大学,南宁 530001广西中医药大学附属瑞康医院,南宁 530011广西中医药大学附属瑞康医院,南宁 530011
生物科学
类风湿关节炎SD大鼠胶原诱导性关节炎佐剂诱导性关节炎
rheumatoid arthritisSD ratcollagen-induced arthritisadjuvant-induced arthritis
《中国实验动物学报》 2026 (5)
685-699,15
2025年中央财政医疗服务与保障能力提升补助资金(中医药事业传承与发展部分)-中西医"旗舰"科室-骨伤科(桂财社函(2025)36号),广西自然科学基金(2024GXNSFAA010321),广西中医药大学A类"桂派中医药传承创新团队"(2022A004),广西中医药大学研究生教育创新计划项目(YCBXJ2025029,YCSY2025060).Funded by 2025 Central Government Subsidy for Enhancing Medical Service and Guarantee Capacity(Part of Inheritance and Development of Traditional Chinese Medicine)-Chinese and Western Medicine"Flagship"Department-Orthopedics and Traumatology Department(Guicai Shehan[2025]No.36),Guangxi Natural Science Foundation(2024GXNSFAA010321),Guangxi University of Chinese Medicine Category A"Guipai Chinese Medicine Inheritance and Innovation Team"(2022A004),Innovation Project of Guangxi Graduate Education of GXUCM(YCBXJ2025029,YCSY2025060).
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