臺灣博碩士論文加值系統

腎臟移植後，受贈者的腎功能逐步下降仍是不可避免的現象。造成移植腎功能下降的原因可能是慢性的發炎反應和動脈粥樣硬化。內皮細胞特異性分子-1 (endothelial cell-specific molecule-1) 是一種蛋白醣 (proteoglycan)，也稱為endocan，表達於腎臟的內皮細胞中，在炎症反應時會顯著增加，因此，它可以作為內皮細胞活化的標誌物。本實驗的目的是探討腎臟移植受贈者的慢性腎病可否以血清中endocan 的含量作為早期預測指標。我們的實驗分為體外實驗和體內實驗兩部份進行。體外實驗部份：我們建立了內皮細胞初代 (primary) 細胞培養的系統，將人類臍靜脈內皮細胞（human umbilical vein endothelium cell, HUVEC）培養於不同濃度的α腫瘤壞死因子 (tumor necrosis factor-α, TNF-α）中模擬發炎模式，我們證實TNF-α誘導的發炎內皮細胞會隨時間而增加endocan的分泌。體內實驗部份：為了在病患體中證實此現象，我們招募了97位腎臟移植的受贈者，他們的平均年齡為43.6 ± 13.2歲，平均追蹤時間為7.0 ± 5.7年。發現腎臟移植病患血清中的endocan與TNF-α濃度呈顯著的正相關（r = 0.286, p = 0.002），且越後期之慢性腎臟病患有較高的血清endocan含量（p = 0.077）。經由「接收者操作特徵曲線」(receiver operating characteristic curve, 簡稱ROC曲線) 的統計運算，設定以endocan > 643.19 pg/ml及 endocan ≤ 643.19 pg/ml來區分移植腎功能惡化的可能性（AUC：0.732; 95％，置信區間為0.632 - 0.818）。我們發現，在endocan > 643.19 pg/ml的患者中有較高的血清肌酸酐 (creatinine) 值 （1.6 ± 1.1 mg/dL vs 1.2 ± 0.4 mg/dL, p = 0.029）和較差的腎絲球過濾率。我們的結果證實，移植腎的功能惡化常伴隨著TNF-α及endocan的增加; 因此，endocan可能作為移植病患內皮損傷及腎功能惡化的一個新的標誌。未來將藉此發現，進一步探索其應用性，以利未來移植醫學或慢性腎臟病之臨床應用。

The gradual decline in renal graft function is inevitable in renal transplant recipients. The causes are thought to be chronic inflammation and atherosclerosis. Endocan, also called endothelial cell-specific molecule-1 (ESM-1), is mainly expressed in the endothelial cells in human lung and kidney tissues, is increased in acute and severe inflammation. Thus, it can be considered as a marker for the activation of endothelial cells. We established a primary endothelial cell culture system from human umbilical vein endothelial cells (HUVECs) for the study of the effect with different concentrations of TNF-α on endothelial cells. Endocan was induced in TNF-α-induced inflamed HUVECs. To verify this finding in patients, we recruited 97 renal transplantation recipients and followed for 7.0 ± 5.7 years. The mean age of patients was 43.6 ± 13.2 years and 55.7% (54/97) were male patients. We found that the serum endocan level was correlated with the concentration of TNF-α (r = 0.286, p = 0.002). We also found that the staging of the chronic kidney disease in these patients is positively correlated with the serum endocan level (p = 0.077). After analysis by a receiver operating characteristic (ROC) curve, a concentration of endocan > 643.19 pg/ml was used to differentiate disease progression (AUC: 0.732, 95% confidence interval 0.632 - 0.818). The patients with endocan > 643.19 pg/ml had a higher follow-up creatinine level (1.6 ± 1.1 mg/dL) but lower glomerular filtration rate than those with endocan ≤ 643.19 pg/ml (1.2 ± 0.4 mg/dL, p = 0.029). Our findings suggested that the function of the grafted kidney deteriorated along with the increase of TNF-α and endocan in patient serum. Thus, endocan, an indicator of endothelial injury, may be used as a new biomarker for the deterioration of kidney function in renal transplantation or chronic kidney disease patients.

目錄
中文摘要------------------------------------------------------------------------1
英文摘要------------------------------------------------------------------------3
緒論------------------------------------------------------------------------------4
材料與方法--------------------------------------------------------------------10
結果-----------------------------------------------------------------------------23
討論-----------------------------------------------------------------------------30
參考文獻-----------------------------------------------------------------------36
表目及圖目--------------------------------------------------------------------42
附表-----------------------------------------------------------------------------43
附圖-----------------------------------------------------------------------------47
個人資料-----------------------------------------------------------------------58

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