Department of Anesthesiology, 117850The First People's Hospital of Changzhou, P.R. China.
Department of Anesthesiology, Changzhou Children's Hospital, P.R. China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221125931. doi: 10.1177/09603271221125931.
As a life-threatening respiratory syndrome, acute lung injury (ALI) is characterized by uncontrollable inflammatory activities. Semaglutide (SEM) has been identified as an effective anti-inflammatory drug in a variety of diseases. This study intended to explore the functional effect and potential mechanisms of SEM in ALI.
Lipopolysaccharide (LPS) was used to construct an in vivo ALI model based on Sprague-Dawley (SD) rats and an in vitro ALI model based on human pulmonary artery endothelial cells (HPAECs). Hematoxylin & eosin (H&E) staining and ELISA were applied to evaluate the histopathological changes in pulmonary tissues and detect TNF-α and IL-6 levels. RT-qPCR and Western blotting were used to measure gene and protein expressions in pulmonary tissues and cells. HPAEC viability and apoptosis were evaluated by CCK-8 method and flow cytometry methods.
Semaglutide pretreatment significantly mitigated pulmonary injury, reduced TNF-α and IL-6 production, and led to a decrease in cleaved caspase-3 level and an increase in Bcl-2 level, suggesting SEM could ameliorate LPS-induced ALI in rats. In vitro, SEM increased the proliferative capability and mitigated inflammation and apoptosis in LPS-stimulated HPAECs. In addition, SEM inhibited HDAC5-mediated NF-κB signaling pathway in HPAECs. HDAC5 overexpression or NF-κB signaling activation could partly impair SEM-mediated protective effects against LPS-induced damage to HPAECs.
Semaglutide restrains LPS-induced ALI by inhibiting HDAC5/NF-κB signaling pathway.
急性肺损伤（ALI）作为一种危及生命的呼吸综合征，其特征是不可控的炎症活动。司美格鲁肽（SEM）已被确定为多种疾病中的一种有效抗炎药物。本研究旨在探讨 SEM 在 ALI 中的功能作用及潜在机制。
采用脂多糖（LPS）构建 Sprague-Dawley（SD）大鼠体内 ALI 模型和人肺动脉内皮细胞（HPAEC）体外 ALI 模型，通过苏木精和伊红（H&E）染色和 ELISA 检测肺组织的组织病理学变化，并检测 TNF-α和 IL-6 水平。采用 RT-qPCR 和 Western blot 检测肺组织和细胞中的基因和蛋白表达。通过 CCK-8 法和流式细胞术检测 HPAEC 活力和凋亡。
SEM 预处理显著减轻了肺损伤，降低了 TNF-α和 IL-6 的产生，导致 cleaved caspase-3 水平降低和 Bcl-2 水平升高，表明 SEM 可改善 LPS 诱导的大鼠 ALI。在体外，SEM 增加了 LPS 刺激的 HPAEC 增殖能力，并减轻了炎症和凋亡。此外，SEM 抑制了 HPAEC 中的 HDAC5 介导的 NF-κB 信号通路。HDAC5 过表达或 NF-κB 信号通路激活可部分削弱 SEM 对 LPS 诱导的 HPAEC 损伤的保护作用。
SEM 通过抑制 HDAC5/NF-κB 信号通路抑制 LPS 诱导的 ALI。
