膝骨性关节炎模型的分期特征

Characteristics of knee osteoarthritis models at different stages

目的:通过切断兔的膝前交叉韧带,观察评价其关节炎和滑膜炎不同时期的临床及病理特点,界定膝骨关节炎模型的分期。方法:实验于2004-08/2005-05在解放军南京军区南京总医院动物中心完成,取成年新西兰大白兔30只,将其右膝关节作为实验侧,作膝前交叉韧带切断,左膝关节为对照侧,只作关节囊切开。术后笼中饲养,任其自由活动。分别于造模2,4,6,8及12周时各处死6只。观察滑膜、关节液、软骨的病理特点。采用改良的Mankin骨关节炎的评分法(1～5分定为早期,6～9分为中期,10～14分为晚期)。结果∶28只兔进入结果分析。①实验侧2,4,6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,甲苯胺蓝染色正常或轻染,Mankin评分为2.17～3.8分。②实验侧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,甲苯胺蓝染色不均,Mankin评分为7.83。③实验侧12周可见骨关节炎晚期改变,表现为滑膜部分呈结节样增生,滑液少而混浊,骨赘形成,软骨下骨暴露,软骨细胞减少,甲苯胺蓝大部分失染,Mankin评分为12.2。④对照侧大部分为正常关节软骨(Mankin评分0～1分)。结论∶①兔前交叉韧带断裂后2～6周为骨性关节炎的早期改变,8周为中期,12周为晚期。②此模型能较为全面地反应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。

AIM： To observe and assess the clinical and pathological characteristics of arthritis and synovitis in different phase and make clear the stages of osteoarthritis model by anterior cruciate ligament transection （ACLT） in rabbit knees. METHODS： The experiment was conducted in the Laboratory for Animals, Nanjing General Hospital of Nanjing Military Area Command of Chinese PLA from August 2004 to May 2005. Thirty mature New Zealand white rabbits were the subjects of this study. The right knees were selected as the experiment group in which the ACLT of those knees were resected, and left knees as control group in which only arthrotomy were performed. The rabbits were sent to a large cage, where they were free to move. Six rabbits were killed at the 2^nd, 4^th, 6^th, 8^th and 12^th weeks, respectively. The pathological features of synovium, joint fluid and cartilage were observed. A histologic evaluation was done according to the modified Mankin grading scale （1-5 points as early stage, 6-9 points as middle stage and 10-14 points as advanced stage）. RESULTS： Twenty-eight rabbits were involved in the result analysis. ①The early changes of hypertrophic arthritis at experimental side could be seen at 2^nd, 4^th and 6^th week, which showed hyperplastic synovium, increase exudation, rough surface layer of cartilage, normal or lightly PG staining and score on Mankin as 2.17-3.8 points. ②Intermediate changes were found at the 8^th week at the experimental side, which expressed visible hyperplastic synovium, decrease exudation, fissuration into surface layer of cartilage, disorder arrangement of chondrocytes, ununiformity PG staining and the score of Mankin as 7.83. ③Advanced changes appeared at the 12^nd week at experimental side, which showed hyperplastic synovium by ModUS osteophyte formation, less and clouding synovial fluid, forming osteophyma, exposure of cartilage, chondrocyte decreasing, loss of all cartilage and PG staining, score of Mankin as 12.2. ④Most of the articular cartilage at control side were normal （score of Mankin was 0-1 point）. CONCLUSION： ①After ACLT, early stage changes occur at 2-6 weeks, metaphase at the 8^th week and the advanced stage at the 12^th week. ②This model can more fully reflect the whole process of degeneration of cartilage with osteoarthritis from compensatory hyperplasia at the early period to the decrease of chondrocytes and matrix after loss compensation, from becoming soft of cartilage to denudation and deletion that featured at advanced stage.