臺灣博碩士論文加值系統

巴雷特氏食道症(Barrett’s esophagus)為食道腺癌(esophageal adenocarcinoma)的一種癌前狀態。每年約有0.5%的病人，是由巴雷特氏食道症演變成食道腺癌的狀況。目前在食道醫學，巴雷特氏食道的病人，在病徵輕微極易被忽略；然而，需就醫時，經常已出現嚴重的症狀。在就醫方面主要根據病人敘述的臨床症狀、食道內視鏡檢查食道細胞及病理切片檢查。診斷依據主要為內視鏡有食道化生(endoscopic suspected esophageal metaplasia)，及食道鱗狀上皮細胞(squamous epithelium)被柱狀細胞(columnar epithelium)取代的情形，且有杯狀細胞(goblet cells)產生。目前來說，只能使用內視鏡及切片來協助診斷。蛋白酶激活受體-2(Protease activated receptor 2，PAR-2)在巴雷特氏食道症的表現情形，來做為前瞻性協助診斷的生物標記。本研究使用即時定量聚合酶鏈鎖反應(real-time PCR)檢測在巴雷特氏食道及其他部位的表現量，結果發現PAR-2在巴雷特氏食道的表現量大於正常食道。利用細胞激素與PAR-2做相關性檢測，可得知病人處於發炎期或非發炎期。PAR-2可能是一個很好的生物標記物，可用來協助診斷及追蹤巴雷特氏食道症，在這次實驗中細胞激素對於巴雷特氏食道症的表現，結果顯示IL-10、IL-24、IL-3、COX-2在食道化生區的表現量大於正常食道。除此之外藉由PAR-2與IL-10及PAR-2與COX-2之間的正相關性，我們可以得知胃食道逆流症是一個巴雷特氏食道症的一個因素，其中胰蛋白酶(trypsin)的分泌活化更多的PAR-2，導致病人處於發炎反應，並有可能長期造成鱗狀上皮化生成柱狀上皮的機率升高。另外IL-10與PAR-2的正相關性來進一步得知發炎期的狀態及巴雷特氏症病人的嚴重程度。

Barrett’s esophagus (BE) is precancerous condition of Esophageal Adenocarcinoma (EAC, very often deadly cancer). Every year, about 0.5% of the patients evolved from BE to Esophageal Adenocarcinoma situation. The medicine science to the BE, the patients is easily ignored when the symptom is mild, however when they need for medical treatments, the symptom often becomes serious. In terms of medical examination of the esophagus, they according to the patient described, and doctor were execute esophageal endoscopy and biopsy mainly based on clinical symptoms. The diagnosis of BE is established by endoscopic suspected esophageal metaplasia and replacement of esophageal squamous epithelium by columnar epithelium cells with goblet cells (intestinal metaplasia IM). For now, there were two methods to use endoscopic and biopsy diagnosis BE. This study was designed to compare the different expression of Protease-activated receptor -2 (PAR-2), a potential biomarker for assay the Barrett’s esophagus and EAC. Using real-time polymerase chain reaction to quantitative the PAR-2 expression in BE. We found out that the expression of PAR-2 with BE and stomach were all significantly higher than normal esophagus. By measuring cytokines include interleukin-10, interleukin-24, interleukin-3, Cyclooxygenase-2. We can know that the patient is under the non-inflammatory period or inflammatory period. Protein activated receptor-2 protein may be a good biomarker which can be used to help us to diagnose and manage BE.

目錄
中文摘要 i
Abstract ii
第一章、前言 1
第二章、文獻探討 5
第一節、Barrett食管的介紹 5
第二節、Barrett氏食道症危險因子 6
2.2.1胃食道逆流症(Gastroesophageal Reflux Disease，GERD) 6
2.2.2肥胖 6
2.2.3家族性Barrett氏食道症 7
2.2.4飲食 8
第三節、Barrett氏食道症臨床診斷 8
第四節、內視鏡檢查種類 10
2.4.1食道內視鏡、放大內視鏡(magnify endoscopy) 10
2.4.2窄頻影像技術(NARROW BAND IMAGE, NBI) 11
2.4.3擴大內視鏡(MAGNIFYING ENDOSCOPY) 12
第五節、Barrett氏食道的臨床症狀 12
第六節、Barrett氏食道的治療 13
第七節、PAR-2的介紹 13
第八節、細胞激素介紹 14
第三章、材料與方法 16
第一節、檢體來源與收集 16
3.1.1研究設計 16
3.1.2收案條件 16
3.1.3排除條件 17
第二節、方法與步驟 17
3.2.1電子內視鏡之評估及採集檢體 17
3.2.2組織檢體：組織檢體均質化與RNA的抽取 20
3.2.3反轉錄聚合酶反應(reverse transcriptase polymerase chain reaction，RT-PCR) 22
3.2.4即時定量聚合酶鏈鎖反應(Real-time PCR) 24
3.2.5統計方法 26
第四章、結果 27
第一節、研究對象人口資料分析 27
第二節、病理切片結果 27
第三節、分子生物學實驗結果 27
第四節PAR-2與細胞激素相關性比較 29
第五章、討論 31
第六章、參考文獻 35

圖表目錄
圖一A,B PAR-2在正常食道及巴雷特氏食道及喉嚨、胃部區域mRNA表現情形..38
圖二A,B IL-10在食道及巴雷特氏食道的mRNA表現形…………………………..39
圖三A,B IL-24在食道及巴雷特氏食道的mRNA表現形…………………………..40
圖四A,B IL-3在食道及巴雷特氏食道的mRNA表現形…………………………….41
圖五A,B COX-2在食道及巴雷特氏食道的mRNA表現形…………………………42
圖六PAR-2與IL-10在Barrett氏食道相關性比較………………………………….43
圖七PAR-2與IL-24在Barrett氏食道相關性比較………………………………….44
圖八PAR-2與IL-3在Barrett氏食道相關性比較……………………………………45
圖九PAR-2與COX-2在Barrett氏食道相關性比較…………………………………46

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