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目的:研究干扰素β(interferonβ,IFN-β)在抗胶原Ⅱ功能域抗体诱导的小鼠类风湿性关节炎(rheumatoid arthritis,RA)样模型中的调控作用,探讨RA潜在的干预新靶点。方法:应用抗胶原Ⅱ功能域抗体诱导建立胶原抗体诱导关节炎(collagen antibody induced arthritis,CAIA)小鼠模型,通过其表型、关节评分、免疫组织化学染色、X射线衍射分析是否建模成功,并用IFN-β基因工程药物干预,RANK体外诱导破骨细胞生成,抗酒石酸酸性磷酸酶染色法检测破骨细胞数量,实时荧光定量聚合酶链反应检测RANK/RANKL关键分子变化。结果:CAIA小鼠建模成功,IFN-β能显著缓解CAIA小鼠的病情,实时荧光定量聚合酶链反应显示IFN-β干预后小鼠骨关节中c-FOS、NFATc-1的表达量下降,IFN-β能抑制破骨细胞生成。结论:IFN-β缓解CAIA小鼠模型发病的可能机制是通过RANK/RANKL-IFN-β-NFATc-1下调破骨细胞的生成。
OBJECTIVE: To study the regulatory effect of interferon β (IFN-β) on mouse rheumatoid arthritis (RA) -like model induced by anti-collagen Ⅱ domain antibody and explore the potential new target of RA intervention . Methods: A mouse model of collagen antibody induced arthritis (CAIA) was established by anti-collagen Ⅱ domain antibody. Through modeling of phenotype, joint score, immunohistochemical staining and X-ray diffraction, Interfering with IFN-β gene engineering drugs, osteoclasts were induced by RANK in vitro, the number of osteoclasts was detected by tartrate-resistant acid phosphatase staining, and the key molecular changes of RANK / RANKL were detected by real-time fluorescence quantitative polymerase chain reaction. Results: The model of CAIA mice was successfully established, IFN-β could significantly relieve the CAIA mice, and the expression of c-FOS and NFATc-1 in osteoarthritis of mice decreased after IFN-β intervention by real-time fluorescence quantitative polymerase chain reaction , IFN-β can inhibit osteoclastogenesis. CONCLUSION: The possible mechanism of IFN-β alleviating the pathogenesis of CAIA mouse model is to down-regulate osteoclast formation by RANK / RANKL-IFN-β-NFATc-1.