Inserm, U700, Université Paris 7, Faculté de Médecine Denis Diderot-site Bichat, BP416, 75870 Paris Cedex 18, France.
Expert Opin Ther Targets. 2010 Mar;14(3):329-46. doi: 10.1517/14728221003629750.
Oxidative stress has been implicated in the pathogenesis of pulmonary emphysema. Nuclear factor erythroid-2-related factor 2 (Nrf2) a major antioxidant transcription factor could play a protective role in pulmonary emphysema.
Nrf2 is ubiquitously expressed throughout the lung, but is predominantly found in epithelium and alveolar macrophages. Evidence suggests that Nrf2 and several Nrf2 downstream genes have an essential protective role in the lung against oxidative stress from environmental pollutants and toxicants such as cigarette smoke, a major causative factor for the development and progression of pulmonary emphysema. Application of Nrf2-deficient mice identified an extensive range of protective roles for Nrf2 against the pathogenesis of pulmonary emphysema. Therefore, Nrf2 promises to be an attractive therapeutic target for intervention and prevention strategies.
In this review, we discuss recent findings on the association of oxidative stress with pulmonary emphysema. We also address the mechanisms of Nrf2 lung protection against oxidative stress based on emerging evidence from experimental oxidative disease models and human studie.
The current literature suggests that among oxidative stress targets, Nrf2 is a valuable therapeutic target in pulmonary emphysema.
氧化应激与肺气肿的发病机制有关。核因子红细胞 2 相关因子 2(Nrf2)是一种主要的抗氧化转录因子,可能在肺气肿中发挥保护作用。
Nrf2 在肺部广泛表达,但主要存在于上皮细胞和肺泡巨噬细胞中。有证据表明,Nrf2 和几个 Nrf2 下游基因在肺中对环境污染物和有毒物质(如香烟烟雾)引起的氧化应激具有重要的保护作用,香烟烟雾是肺气肿发展和进展的主要原因。Nrf2 缺陷小鼠的应用确定了 Nrf2 对肺气肿发病机制的广泛保护作用。因此,Nrf2 有望成为干预和预防策略的有吸引力的治疗靶点。
在这篇综述中,我们讨论了氧化应激与肺气肿之间的关联的最新发现。我们还根据实验性氧化疾病模型和人类研究的新证据,探讨了 Nrf2 肺保护对抗氧化应激的机制。
目前的文献表明,在氧化应激靶点中,Nrf2 是肺气肿的一个有价值的治疗靶点。