Rogers Lynette K, Cismowski Mary J
Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus Ohio.
Center for Cardiovascular Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus Ohio.
Curr Opin Toxicol. 2018 Feb;7:37-43. doi: 10.1016/j.cotox.2017.09.001. Epub 2017 Sep 19.
As eukaryotic life evolved, so too did the need for a source of energy that meets the requirements of complex organisms. Oxygen provides this vast potential energy source, but the same chemical reactivity which provides this potential also can have detrimental effects. The lung evolved as an organ that can efficiently promote gas exchange for the entire organism but as such, the lung is highly susceptible to its external environment. Oxygen can be transformed through both enzymatic and non-enzymatic processes into reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can lead to protein, lipid, and DNA damage. Under normal conditions ROS/RNS concentrations are minimized through the activity of antioxidants located both intracellularly and in the epithelial lining fluid of the lung. Oxidative stress in the lung results when the antioxidant capacity is overwhelmed or depleted through external exposures, such as altered oxygen tension or air pollution, or internally. Internal sources of oxidative stress include systemic disease and the activation of resident cells and inflammatory cells recruited in response to an exposure or systemic response. Pulmonary responses to oxidative stress include activation of oxidases, lipid peroxidation, increases in nitric oxide, and autophagy. These internal and external exposures with the subsequent pulmonary responses contribute to development of diseases directly linked to oxidative stress. These include asthma, COPD, and lung cancers. While the vulnerability of the lung to oxidative stress is acknowledged, few effective preventative strategies or therapeutics are currently available.
随着真核生物的进化，对满足复杂生物体需求的能量来源的需求也在增加。氧气提供了这种巨大的潜在能量来源，但提供这种潜力的相同化学反应性也可能产生有害影响。肺作为一种能够有效促进整个生物体气体交换的器官而进化，但正因如此，肺极易受到其外部环境的影响。氧气可以通过酶促和非酶促过程转化为活性氧（ROS）和活性氮（RNS），这可能导致蛋白质、脂质和DNA损伤。在正常情况下，通过细胞内和肺上皮衬液中的抗氧化剂的活性，ROS/RNS浓度会降至最低。当抗氧化能力因外部暴露（如氧张力改变或空气污染）或内部因素而不堪重负或耗尽时，肺部就会产生氧化应激。氧化应激的内部来源包括全身性疾病以及因暴露或全身反应而募集的驻留细胞和炎症细胞的激活。肺部对氧化应激的反应包括氧化酶的激活、脂质过氧化、一氧化氮增加和自噬。这些内部和外部暴露以及随后的肺部反应会导致与氧化应激直接相关的疾病的发展。这些疾病包括哮喘、慢性阻塞性肺疾病（COPD）和肺癌。虽然人们认识到肺对氧化应激的易感性，但目前几乎没有有效的预防策略或治疗方法。
