性别差异对牛Ⅱ型胶原诱导的类风湿关节炎模型的影响  

Effect of gender difference on the model of rheumatoid arthritis induced by bovine typeⅡcollagen

作　　者：孙文婷 万盈盈 杨家煕 王文乾 王皓男 叶婉婷 寇秋爱[1] SUN Wenting;WAN Yingying;YANG Jiaxi;WANG Wenqian;WANG Haonan;YE Wanting;KOU Qiuai(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Beijing University of Traditional Chinese Medicine,Beijing 100029)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]北京中医药大学,北京100029

出　　处：《中国比较医学杂志》2024年第2期25-34,共10页Chinese Journal of Comparative Medicine

基　　金：中国中医科学院优势病种医院制剂新药研发专项(ZZ15-XY-PT-07)。

摘　　要：目的构建雌性及雄性牛Ⅱ胶原诱导的关节炎(collagen-induced arthritis,CIA)模型,比较性别差异对CIA模型关节及关节外表现的影响。方法选用雌性及雄性SD大鼠并注射牛Ⅱ型胶原和弗氏完全佐剂诱导CIA模型,评估各组大鼠的一般情况、关节炎指数、足肿胀度、血清炎症因子及纤溶酶原激活物抑制剂水平、脾指数、膝关节及踝关节病理、右后足爪骨破坏情况、肺间质病变情况。结果雌性CIA大鼠的关节炎指数在初次免疫后第21天较雄性CIA大鼠显著升高(P<0.05),但两组足肿胀度在观察的任一时间点均无显著差异(P>0.05);雌性CIA大鼠血清肿瘤坏死因子α、白介素1β和脾指数均较雄性CIA大鼠显著升高(P<0.05,P<0.001),纤溶酶原激活物抑制剂水平无显著差异(P>0.05);雌性CIA大鼠膝关节和踝关节病理的炎症细胞浸润及滑膜增生评分较雄性CIA大鼠显著升高(P<0.05),雌性CIA大鼠膝关节软骨损伤及右后足爪骨破坏程度均较雄性显著升高(P<0.05);雌性和雄性CIA大鼠均出现了肺间质炎症细胞浸润及轻度纤维化,但雌性比雄性的肺间质病变更重。结论使用SD大鼠构建的雌性及雄性CIA模型均能兼具关节炎及肺间质病变,但雌性CIA大鼠的病变程度更重,在使用CIA模型进行RA相关研究时应关注性别差异带来的影响。Objective To establish female and male bovine collagen-induced arthritis(CIA)models and compare the effects of gender differences on joint and extra-articular manifestations of the CIA model.Methods The CIA model was induced by injection of bovine typeⅡcollagen and Freund’s complete adjuvant into female and male SD rats.The general condition,arthritis index,foot swelling,serum proinflammatory factors and plasminogen activator inhibitor levels,spleen index,knee and ankle joint pathologies,right rear paw bone destruction,and pulmonary interstitial lesions were evaluated.Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on day 21 after initial immunization(P<0.05),but no significant difference was found in the degree of foot swelling between the two groups at any time point(P>0.05).Serum tumor necrosis factorα,interleukin-1β,and the spleen index of female CIA rats were significantly higher than those of male CIA rats(P<0.05,P<0.001).No significant difference was found in plasminogen activator inhibitor levels(P>0.05).The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathologies of female CIA rats were significantly higher than those of male CIA rats(P<0.05),and cartilage damage of the knee joint and bone damage of the right rear paw of female CIA rats were significantly higher than that of male rats(P<0.05).Both male and female CIA rats showed pulmonary interstitial inflammatory cell infiltration and mild fibrosis,but the pulmonary interstitial lesions in females were more severe than those in males.Conclusions Female and male CIA models established in SD rats have arthritis and pulmonary interstitial lesions,but the lesion degree in female CIA rats is more serious.When using CIA models for RA-related research,attention should be focused on the effect of gender differences.

关 键 词：类风湿关节炎 性别差异 牛Ⅱ型胶原诱导的关节炎模型 间质性肺病 

分 类 号：R-33[医药卫生]