胶原诱导Wistar和Lewis大鼠类风湿关节炎模型病理特点的比较  

Comparison of pathological characteristics of Wistar and Lewis rat models of collagen-induced rheumatoid arthritis

作　　者：施佳君 陈方明[1] 马全鑫 陈诚[1] 陈姣姣 郁晨 陈民利[1] SHI Jiajun;CHEN Fangming;MA Quanxin;CHEN Cheng;CHEN Jiaojiao;YU Chen;CHEN Minli(Institute of Comparative Medicine/Laboratory Animal Research Center,Zhejiang Chinese Medical University, Hangzhou 310053,China)

机构地区：[1]浙江中医药大学比较医学研究所动物实验研究中心,杭州310053

出　　处：《中国比较医学杂志》2018年第4期19-26,37,共9页Chinese Journal of Comparative Medicine

基　　金：浙江省科技计划项目(2017C37180);浙江中医药大学比较医学创新团队(XTD201301)

摘　　要：目的探讨牛Ⅱ型胶原(CII)诱导Wistar和Lewis大鼠类风湿关节炎(RA)模型的病症表现与病理特点的差异性。方法采用尾根部皮内注射与CFA混合液进行首次免疫,14 d时注射牛2型胶原(CII)与弗氏完全佐剂(IFA)混合液加强免疫,建立Wistar和Lewis大鼠RA模型,观察Wistar-RA组和Lewis-RA组发病情况,测定足肿胀度和血清抗CII抗体效价水平,在第12周进行足趾形态和组织的病理学检查,测定踝关节滑膜VEGF、IL-6、IL-10和IL-17A的表达。结果胶原诱导后,Wistar与Lewis大鼠分别在第10天和14天出现后足肿胀,第21天和24天达到高峰,血清抗CII抗体效价第3周后显著升高(P<0.01),关节炎指数(AI)明显升高(P<0.01);WistarRA组的成模率80%,第5周足肿胀消退并进入平缓期,Lewis-RA组的成模率100%,第7周足肿胀消退并进入平缓期;在12周时两模型组均发现关节严重软骨侵蚀、滑膜增生以及炎症细胞浸润,关节滑膜血管新生和血管翳形成,后肢股骨和胫骨骨密度明显降低(P<0.01),关节滑膜中VEGF、IL-6、IL-17A表达显著增加(P<0.05,P<0.01),IL-10表达明显下降(P<0.01)。与Wistar-RA组比较,Lewis-RA组足容积和足掌厚度增长持续时间较长,AI高于Wistar-RA组,滑膜血管新生和血管翳形成更明显,踝关节滑膜VEGF表达显著高于Wistar-RA组(P<0.05),而IL-17A表达显著低于Wistar-RA组(P<0.05)。结论 Wistar-RA模型和Lewis-RA模型均出现关节肿胀、变形、活动减少等症状,关节炎指数升高,关节滑膜中VEGF、IL-6、IL-17A的表达增加,IL-10表达下降,与临床相符。但Wistar-RA模型肿胀持续时间短,而Lewis-RA模型肿胀持续时间长,关节损伤也更为严重,血管新生和血管翳形成更明显;Wistar-RA模型IL-17A表达高,而Lewis-RA模型则VEGF高表达,这可能与其病理特点有关。Objective To study the differences of symptoms and pathological features of Wistar and Lewis rat models of collagen-induced rheumatoid arthritis.Methods Wistar and Lewis rats were injected with intermixture of bovine TypeⅡcollage and complete Freund’s adjuvant(CFA)for first immunization,then strengthen it after 14 days and observed the incidence of Wistar-RA group and Lewis-RA group.The degree of paws swelling and the titer of serum anti CII antibody were determined.The pathological changes in toe and joint tissues were examined at 12 weeks,and the expressions of VEGF,IL-6,IL-10 and IL-17A in the synovial membrane of ankle joint were detected.Results After collagen induction,the Wistar and Lewis rats showed paw swelling after 10 d and 14 d,and peaked at 21 d and 24 d,the titer of serum anti CII antibody was significantly increased at third week(P<0.01),and arthritis index(AI)was also significantly increased(P<0.01).In the Wistar-RA rat group,the rate of molding was 80%,and at fifth weeks,the swelling of the paws subsided and went into a flat level.The molding rate of the Lewis-RA group was 100%,at the seventh week,the swelling of paws subsided and went into a flat level.At 12 weeks,the two model groups showed severe articular cartilage erosion,synovial hyperplasia and inflammatory cell infiltration,neovascularization and pannus formation in the joint synovium,and the bone mineral density of the femur and tibia of the hind limbs was significantly decreased(P<0.01).The expression of VEGF,IL-6 and IL-17A in synovium was significantly increased(P<0.05,P<0.01).The expression of IL-10 was obviously decreased(P<0.01).Compared with the Wistar-RA group,the paw volume and paw thickness were increased for a longer time in the Lewis-RA group,AI was higher than that of the Wistar-RA group,synovial angiogenesis and pannus formation were more distinct,the expression of VEGF in synovium was significantly higher than that of Wistar-RA group(P<0.05),while the expression of IL-17A was significantly lower than that in the Wi

关 键 词：类风湿关节炎 牛II型胶原 Wistar大鼠 LEWIS大鼠 病理特点 

分 类 号：R-33[医药卫生]