抗TNFα单克隆抗体在II型胶原诱导的关节炎模型中的应用
Application of anti TNF alpha monoclonal antibody in type II collagen induced arthritis model
  
DOI:10.3969/j.issn.1006.7108.2016.08.031
中文关键词:  胶原诱导的关节炎  类风湿关节炎  TNFα  细胞因子
英文关键词:Collagen induced arthritis  Rheumatoid arthritis  TNF alpha  Cytokines
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作者单位
虎松艳1 唐璐2 冯雯雯3 李青南4 王晓东3* 1. 广东食品药品职业学院广州510520 2. 广东省食品药品职业技术学校广州510520 3. 广东药科大学附属第一医院广州523808 4. 广东药科大学生命科学与生物制药学院广州510006 
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中文摘要:
      目的 制备胶原诱导的关节炎(collagen induced arthritis,CIA)模型,对AT132进行药效评价。方法,制备II型胶原诱导的CIA模型,且对新药AT132进行药效评价。HE染色观察膝关节和踝关节的病理变化。ELISA法检测血清中CII、TNFα的表达。流式细胞仪检测小鼠关节滑膜中TNFα、IL-l、IL-6、IL-10的表达。结果(1)模型组小鼠关节表现为小指关节、足爪、足趾肿胀以及变形,AT132组小鼠关节则表现为轻微的红肿。(2)模型组小鼠膝关节和踝关节病理结果表现为炎性细胞的浸润、滑膜增生、血管翳和破骨细胞的出现,软骨和骨的破坏。AT132组病理结果表现为轻微炎性细胞的浸润和滑膜增生。 (3)ELISA法检测结果发现:模型组中CD的表达明显上升,AT132给药组中C II的表达明显下降(P <0. 01)。(4)流式细胞仪检测结果发现:模型组小鼠关节滑膜中TNFα、IL-l、IL-6、IL-10的表达明显增加,AT132组小鼠关节滑膜中TMFα、IL-l、IL-6、IL-10的表达明显降低(P <0.01)。结论 CIA模型造模成功率为100%, AT132能够有效地治疗关节炎小鼠。
英文摘要:
      Objective To prepare CIA model and to evaluate the effect of ATI32. Methods CIA model was induced by type II collagen, and the effect of the new drug AT132 was evaluated. The pathological changes of knee and ankle joint were assessed using HE staining. The expression of C II and TNF alpha was detected by ELISA. The expression of TNF alpha, IL-1,IL-6, IL-10 in mice’s synovial was detected using flow cytometry. Results (1) The CIA mice model group showed swelling and deformation of the little finger joints, feet and toes. Mice treated with AT132 showed a slight swelling of joints. (2) The pathology of knee and ankle joints of CIA model mice showed infiltration of inflammatory cells, synovial hyperplasia, appearance of pannus, emergence of osteoclasts, and cartilage and bone destruction. The pathological results of the AT132 group showed a slight inflammatory cell infiltration and synovial hyperplasia. (3) The ELISA results showed that the expression of C II and TNF alpha in the CIA model group increased significantly, whereas the expression of C II and TNF alpha in the AT 132 treated group decreased significantly. (4) Flow cytometry results showed that the expression of TNF alpha, IL-1, IL-6 and IL-10 at the CIA model mice’s synovial increased significantly, whereas the expression of TNF alpha, IL-1, IL-6 and IL-10 of the AT132 treated mice’s synovial decreased significantly. Conclusion The successful rate of the CIA model was 100%. AT132 is effective in the treatment of arthritis in mice.
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