兔膝骨关节炎模型的建立及评价

目的 通过兔软骨缺损制备兔膝骨关节炎模型并进行评价。方法 将动物按体质量和性别随机分成3组：假手术组，模型组和阳性对照氨基葡萄糖组，每组12只。造模4周后开始灌胃给药，每天1次，连续给药4周。末次给药后，将动物处死，ELISA试剂盒检测血清及关节液中IL-1β和TNF-α水平，对关节软骨和滑膜进行HE染色，并对关节软骨进行Mankin’s评分以评价其损伤情况。结果 与假手术组相比，模型组血清、关节液中IL-1β、TNF-α水平明显升高，而给予氨基葡萄糖可降低血清、关节液中IL-1β、TNF-α水平。HE染色见模型组软骨结构改变、缺损，滑膜有炎细胞浸润；软骨评分明显高于假手术组。给予氨基葡萄糖可以减轻软骨缺损，减少滑膜炎细胞浸润，降低软骨评分。结论 关节软骨钻孔可建立兔膝骨关节炎模型，反映其主要特征，并能通过给予阳性对照药减轻损伤和炎症反应。该模型可用于治疗关节炎药物的评价和筛选。

Establishment and evaluation of a model of osteoarthritis in the rabbit knee

Objective To establish and evaluate a rabbit model of knee osteoarthritis induced by articular cartilage defect. Method The animals were randomly divided into 3 group, the sham group, the model group and the positive control glucosamine group, each group of 12 animals. After 4 weeks, the drugs were administrated intragastrically once daily for 4 weeks. After the last administration, the animals were executed. ELISA kits were used to detect the level of IL-1β and TNF-α in the serum and joint fluid. The articular cartilage and synovial membrane were stained by HE staining. Mankin’s score was used to assess articular cartilage damage. Result Compared with the sham group, the level of IL-1β and TNF-α in the serum and joint fluid of the model group was significantly increased, while that of glucosamine decreased the level of these inflammatory cytokines. HE staining showed the structural changes and defects of cartilage, and the synovial membrane was infiltrated by inflammatory cells in the model group. The score of cartilage was significantly higher than that of the sham group. Glucosamine can reduce cartilage defects, reduce the infiltration of synovitis cells and reduce the score of cartilage. Conclusion Articular cartilage drilling is able to establish the rabbit model of knee osteoarthritis, reflect the main features of osteoarthritis. The injury and inflammation induced by the model can be reduced by administrating with positive drug. Therefore, this model can be used for the evaluation and screening of arthritis drugs.