Department of Anesthesiology, The Ohio State University, Columbus, OH 43210, United States of America.
Department of Anesthesiology, The Ohio State University, Columbus, OH 43210, United States of America; Center for Medical and Engineering Innovation, The Ohio State University, Columbus, OH 43210, United States of America.
Life Sci. 2023 Sep 1;328:121880. doi: 10.1016/j.lfs.2023.121880. Epub 2023 Jun 23.
Pulmonary oxygen toxicity is caused by exposure to a high fraction of inspired oxygen, which damages multiple cell types within the lung. The cellular basis for pulmonary oxygen toxicity includes mitochondrial dysfunction. The aim of this study was to identify the effects of hyperoxic exposure on mitochondrial bioenergetic and dynamic functions in pulmonary cells.
Mitochondrial respiration, inner membrane potential, dynamics (including motility), and distribution of mitochondrial bioenergetic capacity in two intracellular regions were quantified using cultured human lung microvascular endothelial cells, human pulmonary artery endothelial cells and A549 cells. Hyperoxic (95 % O) exposures lasted 24, 48 and 72 h, durations relevant to mechanical ventilation in intensive care settings.
Mitochondrial motility was altered following all hyperoxic exposures utilized in experiments. Inhomogeneities in inner membrane potential and respiration parameters were present in each cell type following hyperoxia. The partitioning of ATP-linked respiration was also hyperoxia-duration and cell type dependent. Hyperoxic exposure lasting 48 h or longer provoked the largest alterations in mitochondrial motility and the greatest decreases in ATP-linked respiration, with a suggestion of decreases in respiration complex protein levels.
Hyperoxic exposures of different durations produce intracellular inhomogeneities in mitochondrial dynamics and bioenergetics in pulmonary cells. Oxygen therapy is utilized commonly in clinical care and can induce undesirable decrements in bioenergy function needed to maintain pulmonary cell function and viability. There may be adjunctive or prophylactic measures that can be employed during hyperoxic exposures to prevent the mitochondrial dysfunction that signals the presence of oxygen toxcity.
肺氧中毒是由吸入高分数氧引起的，它会损害肺部的多种细胞类型。肺氧中毒的细胞基础包括线粒体功能障碍。本研究的目的是确定高氧暴露对肺细胞中线粒体生物能和动力学功能的影响。
使用培养的人肺微血管内皮细胞、人肺动脉内皮细胞和 A549 细胞，定量测量线粒体呼吸、内膜电位、动力学（包括运动）以及线粒体生物能在两个细胞内区域的分布。高氧（95%O）暴露持续 24、48 和 72 小时，这与重症监护环境中的机械通气时间相关。
在实验中使用的所有高氧暴露后，线粒体运动都发生了改变。在内膜电位和呼吸参数方面，每种细胞类型在高氧后都存在异质性。ATP 连接的呼吸的分区也与高氧持续时间和细胞类型有关。持续 48 小时或更长时间的高氧暴露会引起最大的线粒体运动改变和最大的 ATP 连接呼吸下降，并提示呼吸复合物蛋白水平下降。
不同持续时间的高氧暴露会导致肺细胞中线粒体动力学和生物能的细胞内异质性。氧气治疗在临床护理中广泛应用，但会引起维持肺细胞功能和活力所需的生物能量功能的不良下降。在高氧暴露期间可能会采用辅助或预防措施，以防止线粒体功能障碍，从而提示存在氧毒性。
