中文摘要
慢性阻塞性肺病(COPD)是一种高发病率及致死率的疾病。气道炎症及其引起的粘液高分泌是COPD发病的重要机制。因此抑制气道炎症是改善COPD的关键环节。研究表明TLR4/MyD88/NF-κB通路与气道炎症密切相关。血府逐瘀汤能改善COPD患者肺部感染,抑制炎症反应发生。但其是否通过调控TLR4/MyD88/NF-κB通路,抑制气道炎症反应而改善COPD尚不明确。本研究采用COPD动物模型,通过ELISA、免疫印迹、PCR、免疫组化等技术,观察血府逐淤汤对气道炎症及气道黏液高分泌的影响,以及对TLR4/MyD88/NF-κB通路相关蛋白表达的调控;并采用通路抑制剂、siRNA干扰等技术,从细胞和整体动物水平研究TLR4信号通路在血府逐瘀汤抑制COPD气道炎症效应中的作用,深入阐释血府逐瘀汤的分子作用机理,为临床COPD治疗提供一个新的思路,亦为后续血府逐瘀汤进一步研究和开发提供科学依据。
英文摘要
Chronic obstructive pulmonary disease (COPD), associated with increased mortality and morbidity, has been a serious threat to health worldwide. Airway inflammation is recognized as the central mechanism in the pathogenesis of COPD. Thus inhibiting airway inflammation has been proposed as a key strategy for COPD treatment. The recent studies have shown that TLR4/MyD88/NF-κB signaling pathway is involved in airway inflammation and contributes to the development of COPD. Traditional Chinese formula Xuefu Zhuyu Decoction (XZD), is proved to be effective in improving pulmonary infection in COPD patients, and could significantly inhibit inflammatory reaction. However, it is not clear that whether XZD exhibit protective effect in COPD through inhibiting airway inflammation by regulating TLR4/MyD88/NF-κB pathway. Aiming to study the mechanism of XZD, COPD animal model will be firstly used to investigate the effect of XZD on the secretion of inflammatory mediators and mucus secreted proteins; Secondly, ELISA, RT-PCR, Western blot, are used to study the effect of XZD on expression of TLR4 pathway-related key proteins and genes; Lastly, the relationship between the protection effect of XZD and regulation of TLR4/MyD88/NF-κB pathway is investigated using pathway inhibitor, RNA interference technology and knockout mice. The project would propose a novel therapeutic strategy for COPD, and provide important scientific basis for application and drug development of XZD.
