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

作　　者：虎松艳[1] 唐璐 冯雯雯[3] 李青南[4] 王晓东[3] 

机构地区：[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

出　　处：《中国骨质疏松杂志》2016年第8期1077-1082,共6页Chinese Journal of Osteoporosis

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-1、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CⅡ的表达明显上升,AT132给药组中CⅡ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-1、IL-6、IL-10的表达明显增加,AT132组小鼠关节滑膜中TNFα、IL-1、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。Objective To prepare CIA model and to evaluate the effect of AT132. Methods CIA model was induced by type II collagen,and the effect of the newdrug 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 flowcytometry. 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 AT132 treated group decreased significantly.（ 4） Flowcytometry 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.

关 键 词：胶原诱导的关节炎 类风湿关节炎 TNFΑ 细胞因子 

分 类 号：R452[医药卫生—治疗学]