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系統識別號 U0026-1602201600204900
論文名稱(中文) 周邊動脈阻塞性疾病患者,其第一型血管細胞黏附分子與腎功能相關性之研究
論文名稱(英文) Association of vascular cell adhesion molecule 1 and renal function in patients with peripheral artery occlusive disease
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 104
學期 1
出版年 105
研究生(中文) 李柏增
研究生(英文) Po-Tseng Lee
學號 S97001019
學位類別 碩士
語文別 英文
論文頁數 36頁
口試委員 指導教授-劉秉彥
口試委員-李貽恆
口試委員-李政翰
中文關鍵字 周邊動脈阻塞性疾病  慢性腎臟病  洗腎  VCAM-1 
英文關鍵字 Peripheral artery occlusive disease  Vascular Adhesion Molecule 1  Chronic kidney disease  hemodialysis 
學科別分類
中文摘要 背景介紹
慢性腎臟病和洗腎是周邊動脈阻塞性疾病的危險因子。在臨床觀察中,周邊動脈阻塞性疾病的患者若合併有慢性腎臟病或洗腎,其周邊動脈阻塞性疾病的臨床嚴重程度也較為顯著。另外,在慢性腎臟病或洗腎的患者中,血清中的sVCAM-1濃度較高者,也是心血管疾病死亡率,以及總死亡率的危險因子。因此,本研究之目的,即是針對在周邊動脈阻塞性疾病合併慢性腎臟病或洗腎的患者,釐清血清或組織中,VCAM-1所佔之地位。
方法
五十一位患有周邊動脈阻塞性疾病的患者加入本研究,這些患者都有接受血管攝影檢查證明其周邊動脈性疾病的存在。這些患者因其腎臟功能,而區分成三組,分別是”正常腎功能組”,”慢性腎臟病組”,”洗腎組”。在這三組患者接受周邊動脈整形術的時候,抽取患者之血液,並且測定患者血清中sVCAM-1濃度。組織方面,與病理科合作,取得不同腎功能組別,因為周邊動脈組織疾病而截肢的人體血管檢體,以免疫組織化學方式染色,並且利用影像分析方式(HistoQuest),測出染上細胞的多寡。接著將這些組織中的VCAM-1萃取出,以ELISA方式做蛋白質定量。藉以量測不同腎功能組別中,血清中sVCAM-1與組織中VCAM-1的多寡。
實驗結果
以臨床嚴重度來看,”洗腎組”的周邊動脈阻塞性疾病臨床上比較嚴重。在”洗腎組”中,血清中的sVCAM-1濃度與其他兩組比較起來明顯較高。免疫組織染色方面,洗腎組的截肢動脈組織染上VCAM-1的比例也較高,並且經過影像分析軟體(HistoQuest)證實。利用膜蛋白萃取技術,將VCAM-1萃取出後,也可以發現在洗腎組中的VCAM-1濃度較高。
結論
此研究彰顯出VCAM-1在腎功能不全,周邊動脈阻塞性疾病上的地位。VCAM-1濃度在慢性腎功能不全患者,以及洗腎患者的血清中和組織上的表現顯著,可以提供解釋為何腎功能不佳患者其周邊動脈疾病的臨床嚴重度較高。更有甚者,現今對於VCAM-1已經有抗體可資治療。釐清VCAM-1在腎功能不全之周邊動脈疾病上所扮演之角色,或可做為發展未來治療之參考。
英文摘要 Introduction
Poor renal function is a known independent risk factor for peripheral artery occlusive disease (PAOD). The clinical severity of PAOD was also more remarkable in patient with poor renal function. In end-stage renal disease (ESRD) patients under hemodialysis (HD), soluble Vascular Cell Adhesion Molecule 1 (sVCAM-1) is an independent predictor of all cause and cardiovascular death. We proposed that VCAM-1 may play a significant role in PAOD patients with poor renal function.

Method
Fifty-one patients with PAOD diagnosed by angiography were recruited, and their serum was obtained before percutaneous transluminal angioplasty. According to the baseline renal function, the recruited patients were divided as “Normal” group, “chronic renal disease (CKD)” group, and “Hemodialysis (HD)” group. Serum was obtained during angiography. The level of sVCAM-1 was analyzed by ELISA. On the other hand, specimens of PAD amputated tissue and traumatic amputated tissue were collected respectively, and immnohistochemical stain was performed to clarify the histopathological role of the sVCAM-1. IHC result was quantified by HistoQuest. VCAM-1 among the tissue was extracted, and then analyzed by ELISA, too.

Results
In PAOD patients, serum level of sVCAM-1 was elevated in the HD group compared with the normal renal function group (p<0.001), and with the CKD group (p=0.02). IHC stain of sVCAM-1 reveals increased positive cells in CKD and HD groups. In the HD group, the VCAM-1 expression was not only in the endothelial cells, but also in the vascular smooth cells. Further image analysis using HistoQuest also confirms the increment in cell population (2.13% in normal renal function group, 4.22% in CKD group and 12.7% in HD group). Moreover, VCAM-1 extracted from the tissue from different groups also showed abundant VCAM-1 within the CKD and HD groups.

Conclusion
The present study emphasizes the importance of vascular cell adhesion molecule VCAM-1 in the pathogenesis of PAOD patients with CKD and ESRD under HD. The soluble form of VCAM-1 and the tissue expression of VCAM-1 was significantly increased in CKD and ESRD under HD group. The clinical presentation also demonstrated the same trend. Patients with CKD and ESRD under HD are prone to have more severe presentation of PAOD, too. In inclusion, VCAM-1 indeed plays an important role in the pathogenesis of PAOD patients with CKD and ESRD patients under HD.
論文目次 Chinese abstract.........1
English Abstract.........2
Acknowledgement..........4
Thesis Contents..........5
Table Contents...........7
Figure Contents..........8
Abbreviation Index.......9
Chapter 1 Introduction...10
1.1 Peripheral artery occlusive disease (PAOD) and chronic renal disease (CKD)...10
1.2 Vascular Cell Adhesion Molecule-1 and its relationship with PAOD........11
1.3 Hypothesis................12
1.4 Specific aims.............12
Chapter 2 Materials and Methods...................14
2.1 Patient source................................14
2.2 Definition of severity of PAOD................14
2.3 Blood sampling................................15
2.4 Tissue sampling...............................15
2.5 Immunohistochemical stain.....................16
2.6 Quantitative analysis of the VCAM-1 immunohistochemistry stain........................16
2.7 VCAM-1 extraction from the preserved tissue...17
2.8 Statistical analysis..........................18
Chapter 3 Results.................................19
3.1 Clinical data analysis........................19
3.1.1 Baseline characteristics....................19
3.1.2 Clinical biochemistry data..................19
3.1.3 Medication..................................20
3.1.4 PAOD clinical severity and PTA procedure....20
3.1.5 Outcome.....................................21
3.2 Serum VCAM-1 concentration....................21
3.3 Immunohistochemical stain of the PAOD tissue..21
3.4 Quantification of tissue VCAM-1 by ELISA in the PAOD tissue............................................22
Chapter 4 Discussion..............................23
Conclusion........................................25
Tables............................................26
Figures...........................................29
References........................................35
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