Department of Intensive Care Unit, Peking University Third Hospital, Beijing, 100191, China.
Department of Intensive Care Unit, Peking University Third Hospital, Beijing, 100191, China.
Biochem Biophys Res Commun. 2020 Apr 9;524(3):575-581. doi: 10.1016/j.bbrc.2020.01.134. Epub 2020 Feb 1.
Inhibiting the production of reactive oxygen species (ROS) in alveolar epithelial cells (AECs) under oxidative distress becomes a new therapeutic strategy for acute respiratory distress syndrome (ARDS). Herein in the present study, we investigated effects of Nox2, the catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase type 2, on LPS-induced epithelium injury in ARDS mice and in human alveolar epithelial A549 cells. Severe lung injury, disruption of alveolar-capillary barrier with the loss of zonula occluden (ZO)-1 and up-regulated expression of Nox2 in AECs were exhibited in ARDS mice. In vitro, LPS induced decreased cell viability coupled with activated Nox2, high level of ROS, and destroyed ZO-1 distribution. Moreover, VAS2870 proved to inhibit Nox2 expression, reduce ROS generation, restore epithelium barrier integrity, and preserve cell viability in LPS-induced A549 cells. These data demonstrate that Nox2/ROS/ZO-1 axis is of great importance in AECs damage induced by LPS, and the utilization of VAS2870 to inhibit this pathway might lighten LPS-induced ARDS.
在氧化应激下抑制肺泡上皮细胞 (AEC) 中活性氧 (ROS) 的产生成为急性呼吸窘迫综合征 (ARDS) 的新治疗策略。在本研究中，我们研究了 NADPH 氧化酶 2 型的催化亚基 Nox2 对 ARDS 小鼠和人肺泡上皮 A549 细胞中 LPS 诱导的上皮损伤的影响。ARDS 小鼠表现出严重的肺损伤、肺泡毛细血管屏障破坏，以及 ZO-1 丢失和 Nox2 在 AECs 中的表达上调。在体外，LPS 诱导细胞活力下降，同时伴有 Nox2 激活、ROS 水平升高和 ZO-1 分布破坏。此外，VAS2870 被证明可抑制 Nox2 表达，减少 ROS 生成，恢复上皮屏障完整性，并维持 LPS 诱导的 A549 细胞活力。这些数据表明，Nox2/ROS/ZO-1 轴在 LPS 诱导的 AEC 损伤中非常重要，利用 VAS2870 抑制该途径可能减轻 LPS 诱导的 ARDS。
