Department of Anesthesiology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu 213000, China; Department of Anesthesiology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu 213000, China.
Department of Anesthesiology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu 213000, China; Department of Anesthesiology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu 213000, China.
Prostaglandins Other Lipid Mediat. 2024 Jun;172:106821. doi: 10.1016/j.prostaglandins.2024.106821. Epub 2024 Feb 17.
Endothelial dysfunction often accompanies sepsis. Sevoflurane (Sev) is a widely used inhaled anesthetic that has a protective effect on sepsis-associated damage. We aimed to elucidate the role of Sev in endothelial dysfunction by using a model of LPS induced HUVECs. Sev increased the viability and decreased the apoptosis of HUVECs exposed to LPS. Inflammation and endothelial cell adhesion were improved after Sev addition. Besides, Sev alleviated LPS-induced endothelial cell permeability damage in HUVECs. RORα served as a potential protein that bound to Sev. Importantly, Sev upregulated RORα expression and inhibited endoplasmic reticulum (ER) stress in LPS-treated HUVECs. RORα silencing reversed the impacts of Sev on ER stress. Moreover, RORα deficiency or tunicamycin (ER stress inducer) treatment restored the effects of Sev on the viability, apoptosis, inflammation and endothelial permeability damage of HUVECs exposed to LPS. Taken together, Sev ameliorated LPS-induced endothelial cell damage by targeting RORα to inhibit ER stress.
内皮功能障碍常伴有脓毒症。七氟醚（Sev）是一种广泛应用的吸入性麻醉剂，对脓毒症相关损伤具有保护作用。我们旨在通过脂多糖（LPS）诱导的人脐静脉内皮细胞（HUVECs）模型来阐明 Sev 在血管内皮功能障碍中的作用。Sev 增加了 LPS 暴露的 HUVECs 的活力，减少了其凋亡。加入 Sev 后，炎症和内皮细胞黏附得到改善。此外，Sev 减轻了 LPS 诱导的 HUVECs 内皮细胞通透性损伤。RORα 作为一种潜在的与 Sev 结合的蛋白。重要的是，Sev 上调了 LPS 处理的 HUVECs 中 RORα 的表达，并抑制了内质网（ER）应激。RORα 沉默逆转了 Sev 对 ER 应激的影响。此外，RORα 缺失或衣霉素（ER 应激诱导剂）处理恢复了 Sev 对 LPS 暴露的 HUVECs 活力、凋亡、炎症和内皮通透性损伤的影响。总之，Sev 通过靶向 RORα 抑制 ER 应激来改善 LPS 诱导的内皮细胞损伤。
