性别差异对牛II型胶原诱导的类风湿关节炎模型的影响
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作者单位:

1.中国中医科学院西苑医院;2.北京中医药大学

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中国中医科学院优势病种医院制剂新药研发专项


Effect of gender difference on the model of rheumatoid arthritis induced by bovine type II collagen
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Affiliation:

1.Xiyuan Hospital,China Academy of Chinese Medical Sciences;2.Beijing University of Chinese Medicine

Fund Project:

Special project for research and development of new drugs in preponderant disease hospitals of the Chinese Academy of Traditional Chinese Medicine

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    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、脾脏指数、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),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、脾脏指数均较雄性CIA大鼠显著升高(P<0.001;P<0.001;P<0.05),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);雌雄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。

    Abstract:

    Objective To construct female and male bovine collagen-induced arthritis (CIA) models and compare the effects of gender differences on the joint and extra-articular manifestations of CIA models. Methods The CIA model was induced by injection of bovine type II collagen and Freund's complete adjuvant into female and male SD rats. The general condition, arthritis index, foot swelling, serum inflammatory factors and plasminogen activator inhibitor levels, spleen index, knee and ankle joint pathology, right rear paw bone destruction, and pulmonary interstitial lesions of rats in each group were evaluated. Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on the 21st day after initial immunization (P<0.05), but there was no significant difference in the degree of foot swelling between the two groups at any time point of observation (P>0.05); Serum tumor necrosis factor α, interleukin1β and spleen index of female CIA rats were significantly higher than those of male CIA rats (P<0.001; P<0.001; P<0.05), there was no significant difference in plasminogen activator inhibitor levels (P>0.05); The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathology of female CIA rats were significantly higher than those of male CIA rats (P<0.05), and the cartilage damage of knee joint and the bone damage of 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. Conclusion Both female and male CIA models constructed with SD rats can have both arthritis and pulmonary interstitial lesions, but the lesion degree of female CIA rats is more serious. When using CIA models for RA related research, attention should be paid to the impact of gender differences.

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  • 收稿日期:2023-02-24
  • 最后修改日期:2023-10-23
  • 录用日期:2024-01-17
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