Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of less than 2.5 µm (PM_2.5) causes respiratory injury mainly due to oxidative stress. Although the fisetin has biological activities such as the antiviral, neuroprotective, and anti-inflammatory activities, the effect of fisetin on PM-mediated oxidative damage has not been studied. In this study, we tested the protective effect of fisetin against PM_2.5-induced toxicity in human pulmonary artery endothelial cells (HPAECs) and its molecular mechanism. Exposure to PM_2.5 decreased cell viability in HPAECs in a time- and dose-dependent manner, possibly due to increased release of extracellular lactate dehydrogenase and generation of intracellular reactive oxygen species (ROS). Cell viability assay demonstrated that treatment of HPAECs with fisetin increased cell viability and reduced PM_2.5-induced oxidative stress in a dose-dependent manner. Serum- and glucocorticoid-inducible kinase 1 (SGK1), a crucial cell survival factor, was downregulated by PM_2.5 which was recovered by fisetin. Furthermore, fisetin treatment inhibited intracellular ROS in HPAECs generated by PM_2.5. Moreover, decreased antioxidant enzymes activities of superoxide dismutase and catalase level in PM_2.5-treated cells were reversed by fisetin treatment. Our results suggest that fisetin effectively protects human HPAECs from PM_2.5-induced oxidative damage via antioxidant effects.

暴露于空气动力学直径小于 2.5 µm (PM _2.5 ) 的高浓度大气颗粒物 (PM ) 会导致呼吸损伤，主要是由于氧化应激。尽管非瑟酮具有抗病毒、神经保护和抗炎活性等生物活性，但尚未研究非瑟酮对 PM 介导的氧化损伤的影响。在这项研究中，我们测试了非瑟酮对 PM _2.5诱导的人肺动脉内皮细胞 (HPAECs) 毒性的保护作用及其分子机制。暴露于 PM _2.5HPAECs 中细胞活力以时间和剂量依赖性方式降低，这可能是由于细胞外乳酸脱氢酶的释放增加和细胞内活性氧 (ROS) 的产生。细胞活力测定表明，用非瑟酮处理 HPAECs 以剂量依赖性方式增加细胞活力并减少 PM _2.5诱导的氧化应激。血清和糖皮质激素诱导激酶 1 (SGK1) 是一种关键的细胞存活因子，它被PM _2.5下调，而 PM _2.5被非瑟酮恢复。此外，非瑟酮处理抑制了 PM _2.5产生的 HPAEC 中的细胞内 ROS 。此外，PM _2.5中超氧化物歧化酶和过氧化氢酶水平的抗氧化酶活性降低-处理的细胞被非瑟酮处理逆转。我们的结果表明，非瑟酮通过抗氧化作用有效保护人类 HPAECs 免受 PM _2.5诱导的氧化损伤。