兔骨性关节炎模型构建及早中晚期的特点

背景：传统的骨性关节炎动物模型因复制时间长、稳定性差、成功率差异大且对骨性关节炎的病程未加详细分析从而限制了其应用。目的：以改良的Hulth造模方式观察膝骨性关节炎不同时期的临床及病理特点，界定膝骨性关节炎模型的分期。方法：无菌条件下暴露兔膝关节内侧纵切口长约2 cm，显露膝关节，然后切断前后交叉韧带及内侧副韧带，完整切除内侧半月板，保留关节软骨面。术后不固定伤肢，自由活动，术后1周内均给予80万单位青霉素预防感染。30 min/d分2次驱赶，连续12周。以不做任何处理兔膝关节为正常对照。造模后 4，6，8，10，12周时Mankin评分及电镜、光镜观察股骨内髁的病理特点。结果与结论：模型组4，6周可见早期骨关节炎的改变，表现为滑膜充血增生，关节渗出增多，软骨表层不平整，基质染色轻染，Mankin评分为3.5~3.8分；8周可见骨关节炎中期改变，表现为滑膜增生明显，滑液少，软骨裂隙形成达表层，软骨细胞排列紊，基质染色不均，Mankin评分为8~9分；12 周可见骨关节炎晚期改变，表现为滑膜严重结节样增生滑液少而浑浊，骨赘形成严重，软骨下骨暴露，软骨细胞减少，基质染色大部分失染，Mankin评分为12~14分。电镜下观察结果与组织学观察结果相符。结果提示以改良hulth法制作骨性关节炎模型，造模后6 周为早期改变，8周为中期，12周为晚期，此模型比较全面地反映了骨性关节炎软骨退变从早期的代偿性增生到失代偿后软骨细胞和基质减少，软骨变软到剥脱缺失为特点的晚期改变的全过程。

Construction and pathological features of a rabbit osteoarthritis model in early, middle, and later phases

BACKGROUND: Application of traditional osteoarthritis animal models was limited by long duplicated time, poor stability, different successful rate, and rough analysis of osteoarthritis. OBJECTIVE: To observe clinical and pathological features of osteoarthritis by modified Hulth modeling way and to determine the stages of osteoarthritis. METHODS: A 2-cm medial longitudinal incision was resected to expose knee joint. Anterior and posterior cruciate ligament and medial collateral ligament were cut off, and medial meniscus was fully cut to reserve articular cartilage. The injured limb was not fixed postoperatively. Animals were allowed to move freely. At one week after surgery, 800 000 U penicillin was used to avoid from infection, 30 min/d, twice per day, for 12 successive weeks. The normal group was treated without any treatments. Pathological features were observed using Mankin scores under electron and optic microscope at 4, 6, 8, 10, and 12 weeks postoperatively. RESULTS AND CONCLUSION: Changes of osteoarthritis were observed in the model group at 4 and 6 weeks after operation, showing synovial hyperemia and hyperplasia, increased synovial fluid effusion, cartilage surface roughness, matrix stained tinge, and Mankin score of 3.5-3.8. Intermediate stage changes of osteoarthritis were found in the model group at 8 weeks after operation, showing synovial hyperplasia, less synovial fluid, fissuration reaching cartilage surface, cartilage cells with tangled and uneven staining matrix, Mankins score of 8-9. Advanced osteoarthritis changes were observed in the model group at 12 weeks after operation, showing severe nodular synovial hyperplasia, less and turbid synovial fluid, osteophyte formation of serious exposure of subchondral bone, cartilage cells reducing the majority of loss of matrix staining, and Mankin score of 12-14. Electron microscopy indicated a coincidence with the histological observation of cell mutation. The rabbit model by Hulth suggested that early change of osteoarthritis occurred at 6 weeks after operation, intermediate stage at 8 weeks, and advanced stage at 12 weeks. This model could be more comprehensive response to osteoarthritis cartilage degeneration from early compensatory hypertrophy to decompensation after the cartilage cells and matrix reduction, cartilage softened to endarterectomy missing characterized the late changes in the entire process.