謝易修李梅蘭Mei-Lan醫學研究所2026-10-289999-12-312005https://handle.ncl.edu.tw/11296/uq7bsrhttps://scholars.csmu.edu.tw/handle/123456789/35113細胞外基質的重建在正常的生長與腎臟的發育過程中扮演一個極重要的生理特性。 MMP-2 和 MMP-9 可使細胞外基質降解，一般相信它在腎臟疾病扮演重要的調控角色。此外，血液循環中的proMMP-2 和 proMMP-9 在腎臟移植的病患所扮演的角色到目前為止還不是很清楚。因此我們利用 gelatin zymography 去分析 353位腎臟移植病患和 50 位健康個案血清中 proMMP-2 和proMMP-9 的濃度。由實驗結果發現，腎臟移植病患的血清creatinine 濃度高於健康個案且 GFR 比健康個案差。並且發現腎臟移植病患 proMMP-2 增高，血清 creatinine 濃度愈高且 GFR 愈差，而 proMMP-9 則與 proMMP-2 的結果相反。在免疫抑制劑的使用方面，我們發現 cyclosporine (CsA) 或 tacrolimus (FK506) 合併 rapamycin 服用的腎臟移植病患，其血清 creatinine 及proMMP-2 濃度高於單獨服用 CsA 或 FK506 的病患。此外 ，也發現腎臟移植病患罹患糖尿病其 proMMP-2 濃度高於沒有糖尿病的病患 。然而，腎移植前使用不同的透析方式並不會影響proMMP-2和 proMMP-9 的濃度。我們也發現在腎移植時間愈久， proMMP-2濃度隨著移植時間會有正相關性存在。根據上述結果可以推論，腎臟間質細胞增生可能分泌大量的 proMMP-2，進而使血清中proMMP-2 濃度愈高，導致腎絲球硬化後無法執行正常的功能。Remodeling of extracellular matrix (ECM) is an important physiologic feature of normal growth and kidney development. Matrix metalloproteinase-2 and -9 (MMP-2 & -9), extracellular matrix degrading enzymes, are believed to involve in renal diseases. However, the contribution of circulating MMP-2 and -9 in the kidney transplant recipients have not yet been elucidated. In this study, together with the determination of serum creatinine, serum levels of proMMP-2 and proMMP-9 were measured by gelatin zymography in 353 kidney transplant recipients and 50 healthy controls to reveal that serum creatinine of kidney transplant recipients was significantly higher than that of healthy controls, but glomerular filtration rate (GFR) was significantly lower than healthy controls. In addition, along with the increase of serum levels of proMMP-2, the serum level of creatinine was increased and GFR was decreased. In contrary, along with the decrease of serum levels of proMMP-2, the serum level of creatinine was increased and GFR was decreased. Among various immunosupression regimens, a combination of rapamycin with cyclosporine (CsA) or tacrolimus (FK506) for kidney transplant recipients could lead to a significantly higher serum creatinine and proMMP-2 concentration, as compared with alone treatmented CsA or FK506. In addition, recipients with diabetes mellitus (DM) and post-transplant diabetes mellitus (PTDM) had significantly higher serum proMMP-2 concentrations compared to patients with DM. Furthermore, serum creatinine, proMMP-2 and proMMP-9 concentrations were not affected by dialysis types of recipients before transplantation. By linear regression, our results indicated a positive correlation of serum proMMP-2 concentration with post-transplantation time in kidney transplant recipients. From these results, it was suggested that the proliferation of kidney mesangial cells could enhance the proMMP-2 production, further increase serum proMMP-2, and in turn leading to glomerulosclerosis end in failure of kidney function.thesis