MMP-2和MMP-9活性与早期类风湿关节炎患者X线侵蚀的关系

目的研究基质金属蛋白酶（MMPs），MMP-2，MMP-9，MMP-14和组织基质金属蛋白酶抑制剂（TIMP）与早期类风湿关节炎患者x线侵蚀改变的关系。方法募集66例早期滑膜炎患者为研究对象。采用酶法测定血清MMP—1，MMP-2，MMP-9，MMP-14和，TIMP—1，TIMP-2的水平，用免疫组化法测定滑膜组织MMP-2，MMP-9及其分子调节荆的表达水平。用明胶酶谱法测定MMP-2，MMP-9的活力。4例健康对照组也进行相应检测。结果RA患者组织MMP-14（MMP-2酶原激活剂）表达明显强于非RA患者（8．4±5）vs（3．7±4）cells／HPF，P〈0．01）]。相反，RA患者中TIMP-2（MMP-2抑制剂）表达低于非RA患者（25±12）vs（39±9）cells／HPF，P〈0．01）]。正常滑膜组织未检测到MMP-2，MMP-14和TIMP-2的表达。滑膜组织侵蚀改变患者MMP-2明显高于非侵蚀性改变者。但MMP-2与MMP-9的组织表达与血清表达不相关。结论MMP-2，MMP-9在RA患者的关节侵蚀性改变进展过程中产生重要作用，推测通过抑制MMP-2和MMP-9活性的治疗策略可延缓或预防关节滑膜的早期侵蚀性改变。

Relationship between activity of Matrix metalloproteinase-2 and Matrix metalloproteinase-9 with radiographic erosions in pafients with early rheumatoid arthritis

Objective To investigate whether the expression and activity levels of MMP-2 and MMP-9, and their regulators MMP-14 and tissue inhibitor of metalloproteinase （TIMP）, are associated with early erosion formation in patients with rheumatoid arthritis or not. Methods A subset of 66 patients was selected from a larger early synovitis cohort on the basis of tissue availability for the study of synovial tissue and serum gelatinase expression. Serum levels of MMP-1, MMP-2, MMP-9, MMP-14, TIMP-1 and TIMP-2 were determined, and synovial tissue was examined by immunohistology for the expression of MMP-2 and MMP-9, and their molecular regulators. Gelatinolytic activity for MMP-2 and MMP-9 was quantified using a sensitive, tissue-based gel zymography technique. Four healthy individuals underwent closed synovial biopsy and their synovial tissues were analyzed. Results Tissue expression of MMP-14 in RA group, the activator for MMP- 2, was significantly higher than that in non-RA patients （8. 4 ±5 versus 3.7±4 cells/high-power field; P 〈0. 01） ]. In contrast, the expression of TIMP-2 in RA group, an inhibitor of MMP-2, was lower than that in the non-RA samples （25 ± 12 versus 39 ± 9 cells/highpower field ; P 〈 0. 01 ） ]. Synovial tissue expressions of MMP-2, MMP-14, and TIMP-2 were virtualty undetectable in normal synovial tissue samples. The synovial tissue samples of patients with erosive disease had significantly higher levels of active MMP-2 than those of patients without erosions. Tissue expression of MMP-2 and MMP-9, however, did not correlate with the serum levels of these enzymes. Condusion We have provided evidence that active MMP-2 complexes are detectable in the inflamed RA synovium and may be involved in the development of early bony erosions. These results suggest the strategy to inhibit the activation of MMP-2 may have the potential for retarding or preventing early erosions in patients with inflammatory arthritis.