Department of Anesthesiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China, 471003.
Department of Anesthesiology, No. 989 Hospital of Joint Logistic Support Force of the Chinese People's Liberation Army, Luoyang 471003, Henan Province, China.
Life Sci. 2021 Jun 15;275:119391. doi: 10.1016/j.lfs.2021.119391. Epub 2021 Mar 24.
Sevoflurane (Sev) has protective effects in acute lung injury (ALI), but the relevant mechanisms are still not fully understood. The present study aimed to determine whether Sev exerts a protective effect on lipopolysaccharide (LPS)-induced ALI by regulating ferroptosis. In this study, we found that Sev could protect mice from lung injury caused by LPS stimulation, including extenuating lung histological damage, pulmonary edema and pulmonary vascular permeability, and the content of inflammatory factors in Bronchoalveolar lavage fluid (BALF), as well as improving the survival rate of ALI mice, which was in line with the effects of ferroptosis inhibitor ferrostatin-1. Simultaneously, Sev could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced ALI to a certain extent. Additionally, the administration of Sev could inhibit ferroptosis caused by LPS, which was manifested by reducing the accumulation of MDA and Fe, and increasing the levels of GSH and GPX4 in the lung tissues of ALI mice. It was also observed in BEAS-2B cells that the increased MDA and Fe levels and the decreased GSH and GPX4 levels caused by LPS could be rescued by ferrostatin-1 and Sev. LPS stimulation compensatory up-regulated heme oxygenase-1 (HO-1) expression in mouse lung tissues and BEAS-2B cells, which could be enhanced by Sev. Moreover, HO-1 depletion could offset the inhibitory effect of Sev on LPS-induced ferroptosis and inflammation in BEAS-2B cells. Taken together, Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia.
七氟醚（Sev）在急性肺损伤（ALI）中有保护作用，但相关机制尚不完全清楚。本研究旨在确定七氟醚是否通过调节铁死亡来发挥对脂多糖（LPS）诱导的 ALI 的保护作用。在本研究中，我们发现七氟醚可以保护小鼠免受 LPS 刺激引起的肺损伤，包括减轻肺组织损伤、肺水肿和肺血管通透性，以及支气管肺泡灌洗液（BALF）中炎症因子的含量，并提高 ALI 小鼠的存活率，这与铁死亡抑制剂 ferrostatin-1 的作用一致。同时，七氟醚可以在一定程度上消除铁死亡诱导剂柠檬酸铁对 LPS 诱导的 ALI 的恶化作用。此外，七氟醚的给药可以抑制 LPS 引起的铁死亡，这表现为降低 MDA 和 Fe 的积累，并增加 ALI 小鼠肺组织中 GSH 和 GPX4 的水平。在 BEAS-2B 细胞中也观察到，LPS 引起的 MDA 和 Fe 水平增加以及 GSH 和 GPX4 水平降低可以被 ferrostatin-1 和七氟醚挽救。LPS 刺激在小鼠肺组织和 BEAS-2B 细胞中代偿性地上调血红素加氧酶-1（HO-1）表达，七氟醚可以增强这种表达。此外，HO-1 耗竭可以抵消七氟醚对 LPS 诱导的 BEAS-2B 细胞中铁死亡和炎症的抑制作用。综上所述，七氟醚通过上调 HO-1 表达抑制铁死亡，从而减轻 LPS 诱导的 ALI，这可能为七氟醚在临床麻醉中的应用提供了一种可能的机制。
