慢性腎病變患者血漿中MMP-2及MMP-9活性表現與腎功能之相關性探討

細胞外基質重建參與了腎臟發育與病理過程，而造成慢性腎病變的主要原因是細胞外基質中膠原蛋白異常堆積及分解所導致，MMP-2及MMP-9是細胞外基質降解的主要酵素，一般相信它在腎臟病理過程中扮演重要角色。許多文獻證實了在老鼠及兔子動物模式中MMPs在腎絲球硬化及間質腎病纖維化扮演重要角色。但目前尚未有文獻探討慢性腎病變患者血漿中MMP-2及MMP-9的濃度變化及血清中肌酸酐(creatinine)的關係。因此我們利用gelatin zymography及 ELISA去分析60位慢性腎病變患者及40位健康個案(對照組)，分析血漿中MMP-2及MMP-9的活性及濃度變化。結果發現在慢性腎病變患者與對照組比較，血清肌酸酐(creatinine)與血漿中MMP-2活性有顯著增加(p<0.001)， MMP-9活性及CCr濃度則有顯著降低 (分別為p<0.05及p<0.01)。另外，血清creatinine濃度與MMP-2利用線性回歸方式分析有明顯正相關(R=0.288，p=0.02) ;而血清creatinine濃度與MMP-9利用線性迴歸方式分析有明顯負相關(R=0.344，p=0.007) 。本研究首次證實了在慢性腎病變患者中MMP-2及MMP-9和血清中creatinine之間的相關性，推論MMP-2及MMP-9可能有助於釐清慢性腎病變的病理機轉。

It has been proven that extracellular matrix turnover is involved in the pathogenesis of various renal fibrosis diseases. Matrix metalloproteinase-2 and -9 (MMP-2 & -9) are the extracellular matrix degrading enzymes that are believed to play important roles in renal diseases. However, the relationship of circulating levels of MMP-2, -9 and serum creatinine in the patients of chronic kidney disease (CKD) has not yet been investigated. In this study, together with the determination of plasma creatinine, plasma levels of MMP-2 and MMP-9 were measured by gelatin zymography and ELISA in the plasma samples of 60 CKD patients and 40 control subjects. This study shows that serum creatinine concentrations and MMP-2 activities were significantly higher (p<0.001) while MMP-9 activity and creatinine clearance (CCr) were significantly lower (p<0.05 and p<0.001, respectively) in CKD patients, as compared with those of control subjects. In addition, serum creatinine concentrations correlated with MMP-2 activity (R=0.288, p=0.02) and inversely correlated with that of MMP-9 (R=0.344, p=0.007). From these result, it was the first study to demonstrate a correlation between MMP-2, -9 and serum creatinine in CKD patients to suggest that MMP-2 and MMP-9 might contribute in the pathogenesis of CKD.