膝关节炎软骨基质金属蛋白酶2、基质金属蛋白酶9表达与MRI表现的相关性

摘要

背景：研究表明，基质金属蛋白酶可降解关节骨与软骨中的胶原、明胶、弹性蛋白、蛋白多糖等细胞外基质大分子，破坏了细胞外基质产生与降解的平衡，是风湿性关节骨及软骨的破坏的重要原因。　　目的：检测了兔膝关节炎软骨基质金属蛋白酶2、基质金属蛋白酶9的表达，分析了两者与MRI表现的相关性。　　方法：选取健康无骨关节炎表现的日本大耳白兔50只，随机分为正常对照组10只和模型组40只。模型组采用前后交叉韧带切断术建立骨关节炎模型，分别在造模后第1，3，5与7周(各10只)，进行MRI检查和软骨基质金属蛋白酶2、基质金属蛋白酶9表达水平测定。　　结果与结论：①MRI检查结果显示，骨关节炎模型兔的软骨破坏日趋明显，MRI分级差异显著(P<0.05)；②模型组软骨基质金属蛋白酶2与基质金属蛋白酶9 mRNA表达明显高于对照组(P<0.05)，基质金属蛋白酶2表达水平在造模后第3周最高(P<0.01)，随后2周略有下降，但仍显著高于对照组(P<0.05)；基质金属蛋白酶9在第5周达到最高表达水平(P<0.01)，第7周模型组基质金属蛋白酶9表达水平下降，但与对照组相比仍有显著性意义(P<0.05)；③各组软骨损伤的MRI分级与基质金属蛋白酶2(R2=0.119，P=0.012)、基质金属蛋白酶9表达皆存在相关性(R2=0.466，P=0.037)。④结果说明，血清基质金属蛋白酶2、基质金属蛋白酶9水平与骨关节炎患者的病情活动及早期关节软骨破坏显著相关，可以作为早期骨关节炎患者的预测指标。%BACKGROUND:Matrix metal oproteinases (MMPs) have been shown to break the balance between the production and degradation of extracel ular matrix by degrading col agen, gelatin, elastin and other macromolecules, which is the leading cause of bone and cartilage damage in rheumatic arthritis. OBJECTIVE:To determine the expression levels of MMP-2 and MM-9 in the rabbit knee osteoarthritis cartilage, and to analyze whether they are related to the early MRI performance. METHODS:Fifty healthy Japanese white rabbits free from osteoarthritis were enrol ed and randomly divided into control group (n=10) and model group (n=40). The anterior and posterior cruciate ligament amputation was adopted to establish the model of osteoarthritis. Subsequently, MRI examination and the expression levels of MMP-2 and MMP-9 were detected at 1, 3, 5 and 7 weeks (n=10 at each time point), respectively. RESULTS AND CONCLUSION:MRI examination showed that more damaged cartilage appeared with time in the rabbit model of osteoarthritis, and significantly different from MRI classification (P<0.05). The expression levels of MMP-2 and MMP-9 mRNA in the model group were always significantly higher than those in the control group (P<0.05);MMP-2 level reached the highest at 3 weeks after modeling (P<0.01), and then presented a slight decline;MMP-9 level peaked at 5 weeks after modeling (P<0.01) and slightly decreased at 7 weeks. MRI classification of cartage injury and expressions of MMP-2 (R2=0.119, P=0.119) and MMP-9 (R2=0.466, P=0.466) were shown to have the correlation. These results il ustrate that the serum levels of MMP-2 and MMP-9 are related to the early destruction of articular cartilage in patients with osteoarthritis, and can be used as predictors for early osteoarthritis.