痛風性關節炎患者其關節液中明膠水解酶和胞漿素原活化劑及抑制劑變化與發炎之相關研究

基質金屬蛋白水解酶-2、-9及纖維蛋白溶解系統 (plasminogen activator (PA)/plasmin system) 在細胞外基質的組成及分解過程中扮演很重要的角色，而人類軟骨和滑膜細胞也會分泌及製造這些酵素。最近研究顯示 MMPs 及 u-PA 在各種關節炎的關節液中佔有相當的份量，尤其是發炎性關節炎；而這些報告幾乎都只侷限於類風濕性關節炎。而痛風性關節炎是台灣常見的關節疾病，因此我們收集63個痛風性關節炎的關節液檢體，並分析其 MMP-2、-9、u-PA、suPAR 及PAI-1 的含量，並與臨床數值作比較。我們利用 gelatin zymography 及 ELISA 的分析，發現在痛風性關節炎的關節液中含有較高量的 MMP-9、u-PA、suPAR 及 PAI-1。這其中的 proMMP-9 及 PAI-1 和關節液中的嗜中性白血球，呈現顯著的線性相關。同時，我們也發現在使用非類固醇的抗發炎藥物治療之後，無論嗜中性白血球或關節炎發炎指數 (LAS) 的數值及 proMMP-9 的數值都有明顯的下降。因此，這些結果顯示了 MMPs、u-PA、suPAR 及 PAI-1 在痛風性關節炎中扮演著很重要的角色。所以在治療痛風性關節炎患者方面，除了使用非類固醇的抗發炎藥物的治療來降低患者的疼痛之外，如何降低 MMPs 及PA/plasmin system 的含量也許對於關節炎的治療方面可以提供更大的幫助。

MMP-2, -9, plasminogen activator (PA)/plasmin system participate in degradation of the extracellular matrix (ECM) components in a variety of arthritis, especially in the inflammatory arthritis. We examined the levels of MMP-2, -9, u-PA, suPAR and PAI-1 in 63 SF from the knee joints of 38 patients with GA and 20 SF from the knee joints of 20 patients with OA and compared them with the clinical and laboratory variables of inflammation. Gelatin zymography revealed that not merely activated MMP-2 levels but proMMP-9 levels in SF from the knee joints of gouty arthritis were associated with the local arthritis activity scores (LAS) (P < 0.001) and correlated well with the neutrophil counts in SF as well (P < 0.001). A similar correlation between proMMP-9 levels and LAS was also found within the individual patients before and during treatment with nonsteroidal antiinflammatory drugs (P < 0.001). Furthermore, the increases of uPA, suPAR and PAI-1 were associated with increased proMMP-9 (P < 0.001, P < 0.001 and P < 0.001, respectively). Increased uPA, suPAR and PAI-1 in SF of GA also correlated to each other (P < 0.001, P < 0.001 and P < 0.001, respectively), and increased PAI-1 corresponded closely with increased leukocyte and neutrophil counts (P = 0.005 and P = 0.004, respectively). Significantly higher uPA, suPAR and PAI-1 (P < 0.001, P < 0.001 and P = 0.012, respectively) appeared in SF of GA than in SF of OA. The analysis of MMP-9 in SF samples can reveal the inflammatory condition of the knee joints with gouty arthritis. Joint aspiration may decrease the amount of MMPs in SF to attack the ECM of joint whether it is normal or not. These results show a correlation of the PA/plasmin system and MMP-9 in SF of GA, resulting in increased PA catalytic activity, and contribute to the inflammation in GA.