移植腎臟纖維化與血清中蛋白水解酵素之相關性探討

Study of Relationships Between Kidney Allograft Fibrosis and Serum Proteinases

林秋菊(Chiu-Chu Lin)

指導教授 ： 謝易修

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2007年)

https://doi.org/10.6834/CSMU.2007.00019

摘要

移植腎功能喪失及慢性移植腎病變是腎臟移植病人最常見移植失敗的原因。慢性移植腎病變的病理特徵是以腎臟纖維化的表現為主。雖然基質金屬蛋白水解酵素(matrix metalloproteinases; MMPs)及纖維蛋白溶解系統(plasminogen activator(PA)/plasmin system)在纖維化的過程中扮演相當重要的角色。但MMPs、u-PA及PAI-1與移植腎臟纖維化的相關性現今仍不清楚。因此，本研究收集50位腎臟移植患者的腎臟組織穿刺切片、血清及尿液為其樣本，首先採用chronic allograft damage index (CADI) score進行移植腎臟纖維化嚴重程度之判讀，再利用gelatin zymography及 ELISA的方式進行血清樣本分析。研究結果發現：腎臟移植時間愈久，其移植腎臟纖維化程度（CADI score）愈嚴重 (p<0.001)，且CADI score與血清PAI-1成正相關性(p=0.003)。臨床醫師在診斷時若能將血清中PAI-1的數值表現，做為移植腎臟纖維化嚴重程度判定之參考依據，將有助於早期發現腎臟移植患者腎臟纖維化之表徵，在適當的時間，提供最適切之醫療診斷與治療，除可提升移植腎臟之存活率外，亦可達到降低醫療資源耗用之目的。

關鍵字

腎臟移植 ； 慢性移植腎病變 ； 基質金屬蛋白水解酵素 ； 纖維蛋白溶解系統 ； 移植腎臟纖維化

並列摘要

The two most common causes of kidney allograft failure are allograft dysfunction and chronic allograft nephropathy (CAN). One way to characterized CAN is by the presence of renal fibrosis. Although matrix metalloproteinases (MMPs) and plasminogen activator (PA)/ plasmin system plays a key role in the progression of renal fibrosis; the exact relationship between kidney allograft fibrosis with MMPs, u-PA and PAI-1 still remains unclear. In trying to correlate kidney allograft fibrosis with the above parameters, fifty kidney transplant recipients were enlisted in our study. Samples were collected from the recipients’ kidney allograft tissue obtained from percuataneous renal biopsy, serum and urine. The chronic allograft damage index (CADI) score was adopted as a measurement of kidney allograft fibrosis. MMP-2 and MMP-9 activity was measured by a method based on gelatin zymography, while u-PA and PAI-1 levels were detected with ELISA. Our results demonstrate that after a period of time, kidney allograft fibrosis severity increased with increasing transplantation duration (p<0.001), in addition, there is a linear dependence between CADI score and serum PAI-1 (p=0.003). The current study suggests clinicians can use correlated serum PAI-1 data as a mean to diagnose CAN and determine the severity of kidney allograft fibrosis. By developing an early detection method, the survival rate for CAN patients may be increased significantly.

並列關鍵字

kidney transplantation ； chronic allograft nephropathy (CAN) ； matrix metalloproteinases (MMPs) ； plasminogen activator (PA) ； u-PA ； PAI-1 ； chronic allograft damage index (CADI) score ； kidney allograft fibrosis

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