Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Compr Physiol. 2011 Jul;1(3):1365-81. doi: 10.1002/cphy.c100068.
Acute lung injury (ALI) and its more severe form of clinical manifestation, the acute respiratory distress syndrome is associated with significant dysfunction in air exchange due to inflammation of the lung parenchyma. Several factors contribute to the inflammatory process, including hypoxia (inadequate oxygen), hyperoxia (higher than normal partial pressure of oxygen), inflammatory mediators (such as cytokines), infections (viral and bacterial), and environmental conditions (such as cigarette smoke or noxious gases). However, studies over the past several decades suggest that oxidants formed in the various cells of the lung including endothelial, alveolar, and epithelial cells as well as lung macrophages and neutrophils in response to the factors mentioned above mediate the pathogenesis of ALI. Oxidants modify cellular proteins, lipids, carbohydrates, and DNA to cause their aberrant function. For example, oxidation of lipids changes membrane permeability. Interestingly, recent studies also suggest that spatially and temporally regulated production of oxidants plays an important role antimicrobial defense and immunomodulatory function (such as transcription factor activation). To counteract the oxidants an arsenal of antioxidants exists in the lung to maintain the redox status, but when overwhelmed tissue injury and exacerbation of inflammation occurs. We present below the current understanding of the pathogenesis of oxidant-mediated ALI.
急性肺损伤（ALI）及其更严重的临床表现，急性呼吸窘迫综合征，由于肺实质的炎症导致空气交换功能显著障碍。有几个因素导致炎症过程，包括缺氧（氧气不足）、高氧（高于正常氧分压）、炎症介质（如细胞因子）、感染（病毒和细菌）和环境条件（如香烟烟雾或有害气体）。然而，过去几十年的研究表明，在肺的各种细胞中形成的氧化剂，包括内皮细胞、肺泡细胞和上皮细胞以及肺巨噬细胞和中性粒细胞，对上述因素的反应，介导了 ALI 的发病机制。氧化剂会修饰细胞蛋白、脂质、碳水化合物和 DNA，导致其功能异常。例如，脂质的氧化会改变膜的通透性。有趣的是，最近的研究还表明，氧化剂的时空调节产生在抗菌防御和免疫调节功能（如转录因子激活）中起着重要作用。为了对抗氧化剂，肺中存在一系列抗氧化剂来维持氧化还原状态，但当氧化剂过多时，就会发生组织损伤和炎症加重。我们下面介绍目前对氧化剂介导的 ALI 发病机制的理解。
