Appolonia Corynn N, Wolf Kaelin M, Zawatsky Charles N, Cinar Resat
Section on Fibrotic Disorders, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States.
Front Physiol. 2022 May 24;13:860449. doi: 10.3389/fphys.2022.860449. eCollection 2022.
Heavy alcohol drinking has negative health effects in multiple organs. It predisposes lungs to inflammatory conditions associated with acute lung injury and increased incidence of pneumonia and sepsis, which may lead to death due to acute respiratory distress syndrome in some individuals with alcohol use disorder (AUD). In general, rodent models of alcohol exposure either do not recapitulate multiple organ injuries as seen in humans or require longer duration to establish tissue injury and inflammation. The recently introduced NIAAA model of alcohol-induced liver injury, characterized by a marked increase in steatosis and liver damage with 10 days of a liquid diet containing 5% ethanol followed by a single ethanol binge (5 g/kg). Therefore, we employed this model to explore the status of surfactant phospholipids, oxidative stress, tissue injury markers and inflammatory cytokines in lungs. In lungs of C57BL/6J mice, the alcohol feeding significantly increased levels of the surfactant phospholipid dipalmitoyl phosphatidylcholine (DPPC) as well as the truncated oxidized phosphatidylcholines palmitoyl oxovaleryl phosphatidyl-choline (POVPC), palmitoyl glutaryl phosphatidyl-choline (PGPC), palmitoyl oxo-nonanoyl phosphatidyl-choline (ALDO-PC), and palmitoyl azelaoyl phosphatidyl-choline (PAzePC) at 9 h post-binge. Additionally, gene expression of the enzymes catalyzing lipid oxidation, such as arachidonate 15-lipoxygenase (Alox15), prostaglandin synthase 2 (Ptgs2), Cytochrome P450 2E1 (Cyp2E1) and NADPH oxidase 1 (Nox1) were significantly increased. Furthermore, ethanol increased levels of the inflammatory cytokine Interleukin-17 in bronchoalveolar lavage fluid. In conclusion, the NIAAA alcohol feeding model might be suitable to study alcohol-induced lung injury and inflammation.
大量饮酒对多个器官有负面健康影响。它使肺部易患与急性肺损伤相关的炎症性疾病，并增加肺炎和败血症的发病率，在一些酒精使用障碍（AUD）患者中，这可能导致因急性呼吸窘迫综合征而死亡。一般来说，酒精暴露的啮齿动物模型要么不能重现人类所见的多器官损伤，要么需要更长时间来建立组织损伤和炎症。最近引入的美国国立酒精滥用与酒精中毒研究所（NIAAA）酒精性肝损伤模型，其特征是在给予含5%乙醇的液体饮食10天，随后单次暴饮乙醇（5克/千克）后，脂肪变性和肝损伤显著增加。因此，我们采用该模型来探究肺表面活性物质磷脂、氧化应激、组织损伤标志物和炎性细胞因子的状况。在C57BL/6J小鼠的肺中，暴饮乙醇后9小时，酒精喂养显著增加了表面活性物质磷脂二棕榈酰磷脂酰胆碱（DPPC）以及截短的氧化磷脂酰胆碱棕榈酰氧戊酰磷脂酰胆碱（POVPC）、棕榈酰戊二酰磷脂酰胆碱（PGPC）、棕榈酰氧壬酰磷脂酰胆碱（ALDO-PC）和棕榈酰壬二酰磷脂酰胆碱（PAzePC）的水平。此外，催化脂质氧化的酶如花生四烯酸15-脂氧合酶（Alox15）、前列腺素合酶2（Ptgs2）、细胞色素P450 2E1（Cyp2E1）和NADPH氧化酶1（Nox1）的基因表达显著增加。此外，乙醇增加了支气管肺泡灌洗液中炎性细胞因子白细胞介素-17的水平。总之，NIAAA酒精喂养模型可能适合用于研究酒精诱导的肺损伤和炎症。
