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应用IFN-β药物干预由抗胶原Ⅱ功能域抗体诱导建立的类风湿性关节炎(rheumatoid arthritis,RA)样小模型(CAIA),揭示RA发病可能的新靶点以及为将IFN-β药物用于RA患者以调节其免疫功能紊乱和骨代谢失衡提供新的理论和实验依据。本研究采用不同浓度的抗胶原Ⅱ功能域抗体诱导BAIB/c小鼠,建立RA样动物模型,通过观察其外观、关节评分以及番红固绿和HE染色并与正常对照组比较来评估该模型的成功建立:采用RT-PCR和免疫组化等技术检测各组模型小鼠与免疫功能紊乱和骨质破坏密切相关的MMP-3、MMP-3/TIMP-1、RANKL及c-Fos分子的表达水平。研究发现CAIA组模型小鼠上述各炎症分子的表达均显著高于对照组小鼠,同时利用重组鼠源性IFN-β调控该模型,发现其能缓解CAIA小鼠的发病情况,证明IFN-β具有使RA样小鼠免疫功能重建以及阻抑模型小鼠骨破坏的生物学作用,为进一步深入研究其调控机制和尽快将IFN-β用于临床RA的治疗奠定了实验基础。
Interfering IFN-β with a small sample of rheumatoid arthritis (RA) -induced model of anti-collagen Ⅱ domain antibody to reveal the possible new targets of RA and the potential role of IFN- In RA patients to adjust their immune dysfunction and bone metabolism imbalance provides a new theoretical and experimental basis. In this study, BAIB / c mice were induced with different concentrations of anti-collagen Ⅱ domain antibody to establish a RA-like animal model, which was evaluated by observing the appearance, joint score, and the staining of Safranine and HE and compared with the normal control group The successful establishment: RT-PCR and immunohistochemistry were used to detect the expression of MMP-3, MMP-3 / TIMP-1, RANKL and c-Fos in immune dysfunction and bone destruction The expression level. The study found that the CAIA model mice expression of the above inflammatory molecules were significantly higher than the control group mice, while the use of recombinant murine IFN-β regulation of the model and found that it can alleviate the incidence of CAIA mice, that IFN-β Has the biological function of reconstructing immune function of RA-like mice and inhibiting the bone destruction of model mice, which lays the foundation for further study of its regulatory mechanism and the application of IFN-β in clinical RA.