Bronchopulmonary dysplasia is a severe and long-term pulmonary disease in premature infants. Hyperoxia-induced acute lung injury plays a critical role in bronchopulmonary dysplasia. Resveratrol is a polyphenolic phytoalexin and a natural agonist of Sirtuin 1. Many studies have shown that resveratrol has a protective effect on hyperoxia-induced lung damage, but its specific protective mechanism is still not clear. Further exploration of the possible protective mechanism of resveratrol was the main goal of this study. In this study, human alveolar epithelial cells were used to establish a hyperoxia-induced acute lung injury cell model, and resveratrol (Res or R), the Sirtuin 1 activator SRT1720 (S) and the Sirtuin 1 inhibitor EX-527 (E) were administered to alveolar epithelial cells, which were then exposed to hyperoxia to investigate the role of Res in mitochondrial function and apoptosis. We divided human alveolar epithelial cells into the following groups: (1) the control group, (2) hyperoxia group, (3) hyperoxia+Res20 group, (4) hyperoxia+Res20+E5 group, (5) hyperoxia+Res20+E10 group, (6) hyperoxia+S2 group, (7) hyperoxia+S2+E5 group, and (8) hyperoxia+S2+E10 group. Hyperoxia-induced cell apoptosis and mitochondrial dysfunction were alleviated by Res and SRT1720. Res and SRT1720 upregulated Sirtuin 1, PGC-1α, NRF1, and TFAM but decreased the expression of acetyl-p53 in human alveolar epithelial cells that were exposed to hyperoxia. These findings revealed that Res may alleviated hyperoxia-induced mitochondrial dysfunction and apoptosis in alveolar epithelial cells through the SIRT1/PGC-1a signaling pathway. Thus, Sirtuin 1 upregulation plays an important role in lung protection.

支气管肺发育不良是早产儿严重且长期的肺部疾病。高氧诱导的急性肺损伤在支气管肺发育不良中起关键作用。白藜芦醇是一种多酚类植物抗毒素，是Sirtuin 1的天然激动剂。许多研究表明，白藜芦醇对高氧所致肺损伤具有保护作用，但其具体保护机制尚不清楚。进一步探索白藜芦醇可能的保护机制是本研究的主要目标。本研究以人肺泡上皮细胞建立高氧诱导的急性肺损伤细胞模型，分别采用白藜芦醇（Res或R）、Sirtuin 1激活剂SRT1720（S）和Sirtuin 1抑制剂EX-527（E）给予肺泡上皮细胞，然后将其暴露于高氧以研究 Res 在线粒体功能和细胞凋亡中的作用。我们将人肺泡上皮细胞分为以下几组：（1）对照组，（2）高氧组，（3）高氧+Res20组，（4）高氧+Res20+E5组，（5）高氧+Res20+E10组、(6)高氧+S2组、(7)高氧+S2+E5组、(8)高氧+S2+E10组。Res 和 SRT1720 可缓解高氧诱导的细胞凋亡和线粒体功能障碍。Res 和 SRT1720 上调了 Sirtuin 1、PGC-1α、NRF1 和 TFAM，但降低了暴露于高氧的人肺泡上皮细胞中乙酰基 p53 的表达。这些发现表明，Res 可能通过 SIRT1/PGC-1a 信号通路缓解高氧诱导的肺泡上皮细胞线粒体功能障碍和细胞凋亡。因此，