Department of Emergency, Ningbo No.2 Hospital. No. 41, Northwest Street, Haishu District, Ningbo, 315010, China.
Department of Pulmonary and Critical Care Medicine, The 987th Hospital of Joint Logistics Support Force of Chinese PLA, Baoji, 721000, China.
BMC Pharmacol Toxicol. 2024 Nov 19;25(1):88. doi: 10.1186/s40360-024-00810-1.
Heat stroke (HS) can lead to the development of pulmonary ferroptosis. The inhibition of pulmonary ferroptosis during HS improves patient prognosis. The aim of this study was to investigate the effects of resveratrol (RES) on heat stress at an ambient temperature of 42 °C.
Heat stress was induced in Beas-2B cells and lung injury was induced in HS rats at an ambient temperature of 42 °C. The anti-oxidative stress and anti-ferroptotic effects of RES were confirmed through tail vein injection of nuclear factor-2 associated factor (Nrf2) shRNA recombinant adeno-associated virus 6 (AAV6-shNrf2).
RES treatment attenuated the upregulation of reactive oxygen species (ROS) and malondialdehyde (MDA) levels and alleviated glutathione inhibition in HS. In addition, RES treatment reduced the accumulation of Fe in heat-stressed Beas-2B cells and increased the ferroptosis resistance-related proteins FTH1, GPX4, and SLC7A11 as well as the anti-oxidative stress pathway proteins Nrf2, NQO1, and HO-1. The antioxidant and anti-ferroptotic effects of RES in heat-stressed Beas-2B cells were effectively reversed upon treatment with Nrf2-IN-1, an Nrf2 pathway inhibitor. In the HS rat model, the antioxidant and anti-ferroptotic effects of RES were reversed by an ambient temperature of 42 °C and relative humidity of 60 ± 5%.
RES effectively protected HS rats from lung injury, inhibited the accumulation of Fe, ROS, and MDA in the lung, and upregulated FTH1, GPX4, SLC7A11, Nrf2, NQO1, and HO-1.
热应激（HS）可导致肺部发生铁死亡。HS 时抑制肺部铁死亡可改善患者预后。本研究旨在探讨白藜芦醇（RES）对 42℃环境温度下热应激的影响。
用 Beas-2B 细胞诱导热应激，用 42℃环境温度诱导 HS 大鼠肺损伤。通过核因子-2 相关因子（Nrf2）短发夹 RNA 重组腺相关病毒 6（AAV6-shNrf2）尾静脉注射，确认 RES 的抗氧化应激和抗铁死亡作用。
RES 治疗减轻了 HS 中活性氧（ROS）和丙二醛（MDA）水平的上调，并缓解了谷胱甘肽的抑制。此外，RES 治疗减少了热应激 Beas-2B 细胞中铁的积累，增加了铁死亡相关蛋白 FTH1、GPX4 和 SLC7A11 以及抗氧化应激途径蛋白 Nrf2、NQO1 和 HO-1。抗氧化应激和抗铁死亡作用。RES 在热应激 Beas-2B 细胞中的作用可被 Nrf2 途径抑制剂 Nrf2-IN-1 有效逆转。在 HS 大鼠模型中，42℃和相对湿度 60±5%逆转了 RES 的抗氧化应激和抗铁死亡作用。
RES 有效保护 HS 大鼠免受肺损伤，抑制肺中铁、ROS 和 MDA 的积累，并上调 FTH1、GPX4、SLC7A11、Nrf2、NQO1 和 HO-1。
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