2014-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656688摘要：背景: 近年來，隨著飲食西化，胃食道逆流症及其相關併發症在台灣的盛行率快速增加，典型症狀包括胃酸逆流、胸口灼熱，常會嚴重影響患者之生活及睡眠品質。造成這些症狀的病理機轉相當複雜，分布於中樞及周邊神經之痛覺受器及感覺神經傳導物質被認為扮演相當重要的角色。近年來引入台灣的多管腔食道內阻抗併酸鹼值檢測，結合傳統酸鹼度及電阻力的偵測，能進一步將逆流分為酸性、微酸及非酸三大類，並且能將傳統非糜爛性胃食道逆流症進一步分為真正非糜爛性胃食道逆流、對酸逆流過敏之食道、對非酸逆流過敏之食道及功能性胸口灼熱等四大類。然而，不同逆流型態之亞型的症狀模式及症狀產生之病因機轉目前仍不清楚。目的: 本研究預計以三年的時間，從臨床與基礎的面向來探討胃食道逆流症中不同逆流型態對於食道過敏、症狀產生之病因機轉、臨床特徵及對新一代長效型質子幫浦抑制劑的治療效果扮演的病態生理角色。方法: 臨床研究方面，我們將集合國內多家醫學中心進行此研究。我們將納入 200 位典型之胃食道逆流症狀之患者，所有患者將接受標準化問卷以瞭解胃酸相關症狀之模式及嚴重度，上消化道內視鏡檢查及切片排除結構問題或其他原因之食道炎，在經過食道壓力檢查後，我們會以二十四小時多管腔食道內阻抗併酸鹼值檢測來偵測食道中各種逆流的型態，酸鹼度，高度與頻率，與各種逆流症狀之關聯性。受試者並將接受質子幫浦抑制劑得喜胃通治療四週，並以問卷評估治療效果。最後，我們將根據以食道阻抗併酸鹼值檢測為主之所有檢查結果進行鑑別診斷，分析國人胃食道逆流症不同亞型之臨床特徵、逆流型態及對新一代長效型質子幫浦抑制劑的治療效果。基礎研究方面，我們將建立急性及慢性酸性或混合逆流之大鼠模式，配合質子幫浦抑制劑治療與否，探討不同逆流型態對於食道組織學、發炎情形、相關痛覺受器及感覺神經傳導物質在周邊及中樞神經表現的影響。最後，我們會嘗試將動物實驗發現之可能參與食道感覺之神經傳導物質或痛覺受器在人類食道切片檢體進行驗證。預測之結果：本研究將有助於了解國人之胃食道逆流症之臨床特徵、主觀症狀及各種逆流型態及對新一代長效型質子幫浦抑制劑的治療效果，對往後的相關治療也提供實證醫學之佐證。此外，本研究將有助於了解不同逆流型態對於症狀產生可能之病因機轉，並對未來胃食道逆流症之藥品開發提供基礎之分子生物學基礎。<br> Abstract: Background: Gastroesophageal reflux disease (GERD) has been associated with a broadspectrum of bothersome symptoms and has a great impact on the quality of life of sufferingpatients. The pathophysiology of reflux symptoms is complex and the treatment response toproton pump inhibitor (PPI) also varies greatly. Nociceptors such as acid-sensitive vanilloidreceptors, protease-activated receptors and substance P have also been implicated in thepathogenesis of neurogenic inflammation and symptom perception in non-erosive refluxdisese (NERD) patients with esophageal hypersensitivity. Multichannel intraluminalimpedance-pH (MII-pH) monitoring, recently introduced into Taiwan, is the most sensitivetechnique for detecting all reflux events, including acidic (pH <4), weakly acidic (pH >4, <7)and non-acidic (pH>7) and MII-pH helps to categorize NERD into four groups: true NERDwith an excess of reflux, hypersensitive esophagus to acid reflux, hypersensitive esophagus tonon-acid reflux and functional heartburn.Objective: This 3 years study aims to investigate the role of different reflux profiles of GERDin the esophageal hypersensitivity, symptom perception, characteristics and treatmentresponses to a long-acting PPI, dexlansoprazole, through both clinical and basic aspects.Methods: We will conduct a multi-center collaborative study and enroll 200 patients withtypical GERD symptoms. All subjects will fill out standard questionnaire for pattern andseverity of GERD symptoms, undergo an upper endoscopy and biopsy to exclude other causesof esophagitis. After esophageal manometry to exclude motility disorders, 24-hour MII-pHmonitoring will be performed to determine the reflux profile and symptom association. Allsubjects will receive PPI treatment with dexlansoprazole for 4 weeks and treatment responsewill be evaluated. For the animal studies, Wistar rats of 8 weeks will be prepared for acute andchronic acid reflux models, acute and chronic mixed reflux models, respectively. PPItreatment will be given to mimic non-acid reflux. Histological changes and expression ofvarious norciceptors and neurotransmitters for esophageal sensation in different refluxprofiles of rat tissue and human esophageal samples will be determined.Expected results: With the help of MII-pH, we will elucidate the clinical characteristics,reflux profiles, symptomatology and treatment response in different subtypes of GERDpatients in Taiwan. This study will also provide important insights for understandingindividual diversity of symptom perception is response to different reflux profiles and mayhelp for future development of novel medication for personalized treatment of GERD.胃食道逆流症非糜爛性胃食道逆流症質子幫浦抑制劑多管腔食道內阻抗 併酸鹼值檢測大鼠模式gastroesophageal reflux diseaseproton-pump inhibitordexlansoprazolemultichannel intraluminal impedance-pH monitoresophageal sensationTRPV-1