臺灣博碩士論文加值系統

腦中風在2001年高居台灣十大死因的第二位，僅次於所有癌症。其主要的致病機轉之一乃來自腦血管的動脈硬化。造成動脈硬化的原因很多，其中包括了長期的無機砷暴露。台灣地區據統計曾有超過50萬的居民曾經長期暴露於高砷濃度井水中並且使得西南沿海地區的居民出現了一種名叫烏腳病的週邊血管疾病。而該地區也就被稱為「烏腳病流行區」。在該地區已有許多癌症包括肺癌、皮膚癌、膀胱癌等，已被証實和砷中毒有關，然而對於砷中毒和腦中風的相關性至今仍莫衷一是。為尋求更進一步的了解，我們進行以醫院為主的病例對照研究。自2002年4月至11月，我們總共收集了100例缺血性腦中風病人，36例來自烏腳病流行區的缺血腦中風病人作為病例組，64例來自非烏腳病流行區符合匹配因子的缺血性腦中風病人作為內對照組，另外，同時收集了71例無中風病史且符合匹配因子的人作為外對照組。每一例研究對象都接受問卷調查，輔以前人進行全台灣井水砷濃度調查結果來推估其砷暴露；另一方面也進行血清中上皮生長因子接受器及尿液中砷甲基化程度以做為砷中毒之生物指標及個體對砷解毒能力之評估。結果顯示各組尿液中總砷含量均低於50μg/l，而且病例組和外對照組間對於砷甲基化能力並無達到統計學上有意義的差異，顯示各組目前都是低砷暴露狀態而且病例組在解毒能力上並無異常。各組間血清上皮生長因子接受器濃度均達到統計學上有意義的差異，然而皆低於100 fm/mL。因此是否有臨床應用價值則須進一步探討。綜合以上結論，高砷暴露對於缺血性腦中風相關性仍須進一步探討，其致病機轉是否會和引起癌症的表現相同而出現上皮生長因子接受器的過度表現則無法証實。

Stroke was the second leading cause of death in Taiwan in 2000 and can be caused by cerebral atherosclerosis. As we know, long-term exposure to arsenic can cause atheroscleoris and lead to peripheral vascular disease such as blackfoot disease (BFD), which is an unique endemic peripheral vascular occlusive disease developed in the southwestern coast of Taiwan. Residents who lived in this so called〝blackfoot disease (BFD) endemic area〞were exposed to drinking water from wells with high arsenic concentration before.
The association of high concentration of arsenic in well water and cancers including bladder, skin, and lung cancers were documented; however, previous studies on the association between arsenic and stroke showed controversial results. To evaluate the association between arsenic and ischemic stroke, we conducted a hospital-based case-control study from April 2002 to November 2002. One hundred acute ischemic stroke patients, including 36 patients from BFD endemic area as cases and 64 matched patients from outside the BFD endemic area as internal controls, were enrolled; and 71 matched persons free of stroke were also as external controls.
Participants received questionnaire interview on drinking water history, tests on serum level of epidermal growth factor receptor (EGFR), and determination of arsenic species in urine as indicators of methylation capacity. Data of arsenic level in well water from a previous survey were used to estimate the arsenic exposure of each individual. The results showed all the individuals had low total arsenic concentration in urine and there were no statistical differences in arsenic methylation capacity between case and external control groups.
There were statistically significant differences in EGFR concentrations among the three groups, but all the levels were less than 15 fm/mL. In conclusion, the association between high arsenic exposure and ischemic stroke should be further explored, and EGFR overexpression was not a biomarker for ischemic stroke.

目 錄
中文摘要………………………………………………………I
英文摘要…………………………………………………….II
誌　　謝…………………………………………………….IV
目 錄………………………………………………………V
圖 目 錄……………………………………………………VII
表 目 錄………………………………………………….VIII
第一章　緒論…………………………………………………1
1-1　前言…………………………………………………….1
1-2研究目的……………………………………………2
1-3研究意義其及其重要性……………………………3
第二章　文獻回顧……………………………………………4
2-1　砷的物理及化學特性………………………………….4
2-2　砷中毒的可能性……………………………………….5
2-3　砷毒與腦中風的相關性……………………………….9
2-4　上皮生長因子接受器蛋白質…………………………11
2-5　砷暴露與體內砷物種濃度及其測量…………………12
2-6　研究的現實背景………………………………………14
第三章 材料與方法……………………………………….15
3-1　研究類型………………………………………………15
3-2　收集研究計畫的個體及檢體…………………………16
3-3　研究材料的測量………………………………………17
3-3-1　檢測病人尿液中之砷含量及其生物種的濃度……17
3-3-2　血清中上皮生長因子接受器蛋白質之測定………18
3-3-3　飲水中砷濃度含量…………………………………19
3-4 統計…………………………………………………20
第四章　結果……………………………………………….21
4-1　研究對象的基本特性…………………………………21
4-2 缺血性腦中風型態的比較……………………………23
4-3 血清EGFR抗體濃度……………………………………24
4-4 尿液中各種砷物種濃度總量與百分比………………25
4-5 含砷井水暴露資料分析………………………………26
4-6 砷井水暴露資料與EGFR及尿液總砷量之分析………27
第五章　討論……………………………………………….28
5-1　EGFR濃度在臨床研究的探討…………………………28
5-2　砷暴露與腦中風的相關性……………………………30
5-3　研究限制………………………………………………31
第六章　結論與建議……………………………………….32
6-1　結論……………………………………………………32
6-2　建議……………………………………………………33
參考文獻…………………………………………………….52
附 錄…………………………………………………….65

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