2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/646002摘要：因為抽菸及老年化的人口持續增加，慢性阻塞性肺病(COPD)預估在2030 年將成為世界上排名第四名的致死疾病。呼吸道阻塞為COPD的一個重要病理現象，針對其症狀的常規藥物為支氣管擴張劑(bronchodilator)，分別為乙二型交感神經刺激劑及抗膽鹼藥物。慢性肺功能下降為COPD 患者的特徵之一，然而目前沒有完全阻止COPD患者慢性肺功能下降的治療方式。從數個臨床試驗結果指出，支氣管擴張劑有減緩肺功能下降的功能，但機制未明。肺氣腫為造成慢性肺功能下降的原因，我們的研究發現投予彈力蛋白酵素以及彈力蛋白酵素(elastase)所誘發表現的胎盤生長因子(PlGF)驅使肺部上皮細胞產生細胞自噬、細胞凋亡及小鼠肺氣腫。另外，過去文獻指出支氣管擴張劑可以調控細胞自噬過程，細胞自噬也參與了包括COPD 等數種肺部疾病的致病機轉。因此我們假設支氣管擴張劑會透過抑制細胞自噬、細胞凋亡以及肺氣腫來減緩COPD 病人慢性肺功能下降。在本研究中，我們將利用肺部細胞經PlGF 處理以及氣管內灌注彈力蛋白酵素動物模式，來評估支氣管擴張劑在由彈力蛋白酵素或PlGF 所引起細胞凋亡、細胞自噬、肺氣腫及慢性肺功能下降過程中所扮演的角色。本研究的結果加上未來臨床檢體佐證可能提供支氣管擴張劑如何減緩慢性肺功能下降的詳細機轉以及潛在的治療COPD 策略。<br> Abstract: Due to the increasing population aging and people with smoking habit,chronic pulmonary obstructive disease (COPD) is predicted to be thefourth leading cause of death worldwide in 2030. Airway obstruction isan important pathological component of COPD. Bronchodilators,including beta2-adrengergic receptor agonist and cholinergic receptorantagonist, are regular therapy drug to relieve symptom of airwayobstruction. Progressive lung function decline is one of feature of COPDpatients. However, to date, there is no definite medication to preventprogressive lung function decline in COPD patients. Several clinical trialsindicate the usage of bronchodilators can ameliorate the deterioration oflung function through unknown mechanism. Emphysema causes lungfunction decline and our studies indicate treatment of elastase andelastase upregulated-placenta growth factor (PlGF) triggers autophagyand apoptosis in lung epithelial cells and emphysema in mice. In addition,previous studies had proved bronchodilators regulate autophagy whichparticipates in pathogenic processes in several lung diseases includingCOPD. Therefore, we hypothesize that bronchodilators may amelioratethe lung progressive function decline in COPD patients via inhibitingautophagy, apoptosis and emphysema. In this study, we will evaluate therole of bronchodilators in elastase or PlGF-induced autophagy, apoptosisand emphysema by PlGF-treated lung cell, PPE intratracheal instillationanimal model. The results in this study and further clinical investigationmay provide detail mechanisms of how bronchodilators ameliorateprogressive lung function decline and offer a new potential therapeuticstrategies for COPD.