慢性阻塞性肺疾病抗氧化治疗的研究进展

慢性阻塞性肺疾病(COPD)是最常见的呼吸系统疾病,其确切的发病机制尚不明确,氧化抗氧化失衡在其发病过程中发挥了重要作用.氧化损伤是COPD的重要发病机制之一.本文对近年来氧化/抗氧化失衡在COPD发病中作用机制及抗氧化治疗的研究进展作一综述.     

蛋白酶/抗蛋白酶系统与慢性阻塞性肺疾病

慢性阻塞性肺疾病（COPD）是一种具有气流受限特征的疾病,气流受限不完全可逆、进行性发展,与肺部对有害气体或颗粒的异常炎症反应有关。气道炎症、氧化/抗氧化失衡、蛋白酶/抗蛋白酶失衡均在COPD发病中起重要作用,但其气流受限的分子机制仍未阐明。近年来,蛋白酶/抗蛋白酶失衡与COPD发病机制的研究有很大进展,本文就此作一综述。     

氧化损伤在慢性阻塞性肺疾病中的作用机制研究进展

慢性阻塞性肺疾病(COPD)是最常见的呼吸系统疾病,其确切的发病机制尚不明确,氧化损伤在其发病过程中发挥了重要作用.氧化损伤是由于体内氧化/抗氧化失衡所至,是慢性阻塞性肺疾病的重要发病机制之一.本研究对近年来COPD发病中氧化损伤作用机制的研究进展作一综述.     

过氧化物酶体增殖物激活受体γ调控抗氧化系统与慢性阻塞性肺疾病

氧化/抗氧化失衡是慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)主要发病机制之一.过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)是一种配体依赖性核受体,具有抗氧化作用.PPARγ的一些配体和辅激活因子PGC-1α能调控活性氧的代谢和抗氧化酶的表达,而它们均通过激活PPARγ而发挥抗氧化作用.PPARγ对抗氧化系统这种重要的调控作用,为COPD的发病和治疗的研究提供了一种新的可行性思路.     

抗氧化维生素与慢性阻塞性肺疾病

氧化/抗氧化失衡是慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)主要的发病机制之一,COPD患者肺部及全身氧化应激增强.维生素A(视黄醇)、维生素C(抗坏血酸)和维生素E(α-生育酚)是人体内重要的非酶系抗氧化维生素,可保护机体免受氧化损伤,维持氧化/抗氧化平衡,在COPD防治中发挥重要作用.     

分泌性白细胞蛋白酶抑制剂与COPD的关系

COPD是严重影响人类健康的多发病之一,其主要特征是气道重塑和动态气体陷闭引起的气流受限,且气流受限呈持续性、进行性发展.其发病机制尚未完全阐明,目前认为,蛋白酶-抗蛋白酶失衡是造成COPD气道重塑及气流不可逆受限的重要原因[1],同时炎症反应及氧化-抗氧化失衡也参与其中。     

痰易净在慢性阻塞性肺疾病患者中的临床应用

慢性阻塞性肺疾病（COPD）是临床常见病和多发病。在其发病机制中氧化／抗氧化系统失衡被认为是COPD发生发展的重要机制，而痰易净（N-乙酰半胱氨酸NAC）具有很强的抗氧化作用，在治疗COPD方面具有一定疗效。     

氧化与抗氧化机制在支气管哮喘发生发展中的作用

支气管哮喘(简称哮喘)是临床常见的呼吸系统疾病,其发病机制复杂,症状明显,对患者健康及生活质量影响较大。目前,哮喘的发病机制尚未完全阐明,主要包括气道慢性炎症、气道高反应性、气道重塑以及气道神经调节失衡等,其中氧化损伤在其发病过程中发挥了重要作用。氧化应激广义上是指机体内氧化与抗氧化水平失衡。哮喘患者气道氧化应激主要来源于体外环境中的促氧化剂、气道炎性细胞渗透、新陈代谢失调以及抗氧化能力下降等。研究表明哮喘患者体内氧化水平升高,抗氧化水平降低。本文就氧化与抗氧化作用机制在哮喘中的一些基础研究与进展作一综述。     

N-乙酰半胱氨酸抗氧化作用在慢性阻塞性肺疾病治疗的进展

慢性阻塞性肺疾病（COPD）是一种以气流受限为特征的疾病。它的发病机制与氧化应激、氧化／抗氧化失衡、气道和肺部炎症、感染、蛋白酶／抗蛋白酶失衡及免疫失衡等有关。治疗上主要是控制急性发作期的症状，但不能逆转疾病的进展。20世纪80年代以来，氧化应激、氧似抗氧化失衡在COPD发病中的作用日益受到重视，有研究表明抗氧化治疗能缓解和（或）抑制COPD患者肺功能的下降，有可能改变疾病的病程。因而寻找有效的抗氧化剂成为COPD防治的一个重点。N乙酰半胱氨酸（NAC）是目前治疗COPD最常用的抗氧化剂。本文就目前COPD与NAC之间氧化及抗氧化作用的关系作一综述。     

模式识别受体在慢性阻塞性肺疾病中的作用

COPD是一种具有气流受限特征的肺部慢性炎症性疾病,其总体人群患病率约为10％,在吸烟人群中达到了50％.据报道,工业化国家引起死亡的疾病中COPD排在第4位,预计到2020年将升至第3位[1].因此,COPD已成为全世界广泛关注的公共卫生问题,但其发病机制尚不完全清楚.目前普遍认为,吸烟是COPD发病的主要原因,此外,感染、环境因素、蛋白酶-抗蛋白酶失衡及氧化-抗氧化失衡等均与COPD发病有关.     

抗氧化剂与慢性阻塞性肺疾病的关系研究进展

氧化／抗氧化失衡是慢性阻塞性肺疾病（COPD）的重要发病机制之一,因此抗氧化剂的应用备受关注。本文综述了抗氧化剂与COPD的关系及国内外COPD抗氧化治疗最新的研究进展。     

Heat shock protein 27 and cyclophilin A associate with the pathogenesis of COPD

Background and objective: COPD is a global disease characterized by chronic bronchitis and obstructive emphysema. Its pathogenesis is not fully understood. This study aimed to use proteomics to provide new insights into the mechanisms of COPD. Methods: Protein lysates were prepared from lung tissue samples harvested from never‐smokers, non‐COPD smokers and COPD smokers, and were analysed using 2‐dimensional gel electrophoresis. Differentially expressed proteins were identified using mass spectrometry. The differential expression of heat shock protein 27 (Hsp27) and cyclophilin A (CyPA) was validated by immunohistochemistry and western blotting. Results: Twenty‐four proteins were identified by mass spectrometry as being differentially expressed among the three groups of subjects. The main functions of these proteins involve basic metabolism, oxidation/reduction, coagulation/fibrinolysis, protein degradation, signal transduction, inflammation and cell growth/differentiation/apoptosis. Proteomic analysis revealed that the expression of Hsp27 and CyPA was upregulated in smokers, and this upregulation was particularly marked in COPD smokers. The variation in expression of Hsp27 and CyPA between the groups was confirmed by immunohistochemistry and western blotting. Conclusions: Hsp27 and CyPA are associated with the pathogenesis of COPD, and smoking contributes to the overexpression of these proteins.     

Fibrotic Response of Tissue Remodeling in COPD

Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) involves diverse processes characterized by epithelial disruption, smooth muscle hypertrophy/hyperplasia, airway wall fibrosis, and alveolar destruction. According to the accepted current theory of COPD pathogenesis, tissue remodeling in COPD is predominantly a consequence of an imbalance between proteolytic and antiproteolytic activities. However, most of the studies carried out during the last few years have focused on mechanisms related to degradation of extracellular matrix (ECM) structural proteins, neglecting those involved in ECM protein deposition. This review revisits some of the latest findings related to fibrotic changes that occur in the airway wall of COPD patients, as well as the main cellular phenotypes relevant to these processes.     

Antioxidant therapies in COPD

Oxidative stress is an important feature in the pathogenesis of COPD. Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-κ B) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression. Specific spin traps such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo. Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.     

呼出气冷凝液中生物标记物在COPD的意义

COPD是全球范围内发病率和病死率最高的疾病之一,目前发病机制尚未明确,主要认为其与气道、肺实质及肺血管的慢性炎症、氧化应激及蛋白酶-抗蛋白酶的失衡有关.呼出气冷凝液可有效收集呼吸过程中气道表面形成的气溶胶和挥发性分子,是检测呼吸道炎症因子的重要标本来源,可反映氧化损伤、炎症以及治疗等导致的气道内环境的变化.应用呼出气冷凝液可对COPD的发生发展及急性加重过程实现无创、简单的监测.     

Functional significance of apoptosis in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disease characterized by an abnormal inflammatory response of the lungs to noxious particles and gases. Cigarette smoking remains a major risk factor in COPD development. Accumulating evidence suggests that apoptosis, a regulated form of cell death, may play an important role in COPD pathogenesis. Increased numbers of apoptotic cells can be detected in lung tissue and airways of human subjects with COPD, relative to normal lungs or those from smokers without COPD. Alveolar wall destruction associated with emphysema development, may involve increased apoptosis of alveolar structural cells. Several intervention-induced apoptotic models (e.g., cigarette smoke, vascular-endothelial growth factor inhibition, and interferon-gamma) cause emphysematous changes in vitro and in vivo. Increased apoptosis in COPD can also imply defects in the normal physiological clearance of apoptotic cells. Additional factors that relate to perpetuation of the pathogenesis of COPD, including protease/antiprotease imbalance, inflammation and oxidative stress, may mutually promote apoptosis or contribute to impaired clearance of apoptotic cells. Given that cigarette smoking is the most common cause of COPD, identification of the pathways of cigarette smoke-induced apoptosis may further the understanding of COPD pathogenesis. However, apoptosis rate is not diminished after cessation of cigarette smoking, indicating that other mechanisms perpetuate apoptosis in COPD. Therefore, understanding functional relationships between apoptosis and protease/antiprotease imbalance, inflammation, oxidative stress and other factors potentially involved in COPD pathogenesis may uncover crucial therapeutic targets.     

Exhaled breath condensate analysis in chronic obstructive pulmonary disease

The increasing focus on airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has led to development and evolution of tools to measure it. Direct assessment of airway inflammation requires invasive procedures, and hence, has obvious limitations. Non-invasive methods to sample airway secretions and fluids offer exciting prospects. Analysis of exhaled breath condensate (EBC) is rapidly emerging as a novel non-invasive approach for sampling airway epithelial lining fluid and offers a convenient tool to provide biomarkers of inflammation. It has definite advantages that make it an attractive and a feasible option. It is a source of mediators and molecules that are the causes or consequences of the inflammatory process. Measurement of such markers is increasingly being explored for studying airway inflammation qualitatively and quantitatively in research studies and for potential clinical applications. These biomarkers also have the potential to develop into powerful research tools in COPD for identifying various pathways of pathogenesis of COPD that may ultimately provide specific targets for therapeutic intervention. The EBC analysis is still an evolving noninvasive method for monitoring of inflammation and oxidative stress in the airways. The limited number of studies available on EBC analysis in COPD have provided useful information although definite clinical uses are yet to be defined. Evolving technologies of genomics, proteomics, and metabonomics may provide deeper and newer insights into the molecular mechanisms underlying the pathogenesis of COPD.