基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究

Immunohistochemical expression and significance of MMP-7,MMP-9,MMP-13 and TIMP-1 in osteoarthritis

[目的]观察骨关节炎关节软骨中MMP-7、MMP-9、MMP-13和TIMP-1的表达,探讨其与软骨退变的关系及可能的作用机制。[方法]选取20例因骨关节炎行关节置换的软骨组织,常规HE染色观察其组织学形态,ABC免疫组化法观察关节软骨MMP-7、MMP-9、MMP-13和TIMP-1的表达,2例因意外受伤截肢患者的正常膝关节软骨标本作为对照。统计采用Mann-Whitney U非参数检验及相关分析。[结果]骨关节炎关节软骨出现裂隙、纤维化,软骨细胞增多、排列紊乱,并出现大量簇聚软骨细胞和肥大软骨细胞。MMP-7和MMP-13在正常软骨全层均呈低表达,但在退变软骨中的表达则明显增多,光密度值行U检验,两组差异有显著性(P<0.01)。在正常与OA软骨的浅层,MMP-9和TIMP-1的表达无显著性差异(P>0.05);但在深层软骨中,OA软骨MMP-9和TIMP-1的表达较正常软骨明显增多,两组差异有显著性(P<0.01)。[结论]MMP-7,13在OA软骨全层表达均多于正常软骨;MMP-9,13仅在OA软骨深层出现过多表达。MMPs与TIMPs的失衡是导致关节软骨发生组织学退变的原因之一。

[Objective] To investigate the relationship between degeneration of cartilage and the expressions of Matrix Metalloproteinase 7 （MMP-7） , Matrix Metalloproteinase 9 （ MMP-9 ）, Matrix Metalloproteinase 13 （ MMP-13 ） and Tissue Inhibitor of Matrix Metalloproteinase l （TIMP-1） in osteoarthritis. [ Method] The histological changes of cartilages by hematoxyllin-eosin staining and immunohistochemical expression of Matrix Metalloproteinase 7 （ MMP-7 ）, Matrix Metalloproteinase 9 （MMP-9）, Matrix Metalloproteinase 13 （MMP-13） and Tissue Inhibitor of Matrix Metalloproteinase 1 （TIMP-1） in osteoarthritis, were studied in 20 osteoarthritis cases and 2 normal controls. All data were statistically analyzed by Mann-Whitney U test and correlation analysis. [ Result] The osteoarthritis cartilage underwent fibroplasias and tearing. The quantity of chondrocyte increased and the clustered and hypertrophic cells came into being. Little immunostaining of MMP-7 and MMP-13 was observed in normal cartilage, while their expressions increased in degenerated cartilage （P 〈 0. 01 ）. Expression of RMP-gand TIMP-1 was the same in normal cartilage （ P 〉 0. 05 ）, superficial layer of the moderate and end-stage osteoarthritis. However, it significantly increased in deep layer （P 〈 0. 01 ）. [ Conclusion] The abnormal expression of MMP-7, MMP-9, MMP-13 and TIMP- 1 was likely to be the pathogenesis of cartilage degeneration.