Ryter Stefan W, Kim Hong Pyo, Nakahira Kiichi, Zuckerbraun Brian S, Morse Danielle, Choi Augustine M K
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Antioxid Redox Signal. 2007 Dec;9(12):2157-73. doi: 10.1089/ars.2007.1811.
The respiratory system, including the lung and upper airways, succumbs to injury and disease through acute or chronic exposures to adverse environmental agents, in particular, those that promote increased oxidative or inflammatory processes. Cigarette smoke and other forms of particulate or gaseous air pollution, allergens, microorganisms infections, and changes in inspired oxygen may contribute to lung injury. Among the intrinsic defenses of the lung, the stress protein heme oxygenase-1 constitutes an inducible defense mechanism that can protect the lung and its constituent cells against such insults. Heme oxygenases degrade heme to biliverdin-IXalpha, carbon monoxide, and iron, each with candidate roles in cytoprotection. At low concentrations, carbon monoxide can confer similar cyto and tissue-protective effects as endogenous heme oxygenase-1 expression, involving antioxidative, antiinflammatory, antiproliferative, and antiapoptotic effects. Lung protection by heme oxygenase-1 or its enzymatic reaction products has been demonstrated in vitro and in vivo in a number of pulmonary disease models, including acute lung injury, cigarette smoke-induced lung injury/chronic obstructive pulmonary disease, interstitial lung diseases, ischemia/reperfusion injury, and asthma/airway inflammation. This review summarizes recent findings on the functions of heme oxygenase-1 in the respiratory system, with an emphasis on possible roles in disease progression and therapies.
呼吸系统，包括肺和上呼吸道，会因急性或慢性接触有害环境因素，尤其是那些促进氧化或炎症过程增加的因素而受到损伤并患病。香烟烟雾以及其他形式的颗粒或气态空气污染、过敏原、微生物感染和吸入氧气的变化都可能导致肺损伤。在肺的固有防御机制中，应激蛋白血红素加氧酶-1构成一种可诱导的防御机制，能保护肺及其组成细胞免受此类损伤。血红素加氧酶将血红素降解为胆绿素-IXα、一氧化碳和铁，它们在细胞保护中都具有潜在作用。在低浓度下，一氧化碳可产生与内源性血红素加氧酶-1表达相似的细胞和组织保护作用，包括抗氧化、抗炎、抗增殖和抗凋亡作用。在包括急性肺损伤、香烟烟雾诱导的肺损伤/慢性阻塞性肺疾病、间质性肺疾病、缺血/再灌注损伤以及哮喘/气道炎症在内的多种肺部疾病模型中，体外和体内实验均已证明血红素加氧酶-1或其酶促反应产物对肺具有保护作用。本综述总结了血红素加氧酶-1在呼吸系统中的功能的最新研究发现，重点关注其在疾病进展和治疗中的可能作用。
