Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
Department of Pediatric, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
Toxicol Sci. 2024 Nov 1;202(1):25-35. doi: 10.1093/toxsci/kfae099.
Hyperoxia-induced acute lung injury (HALI) is a complication of oxygen therapy. Ferroptosis is a vital factor in HALI. This paper was anticipated to investigate the underlying mechanism of wedelolactone (WED) on ferroptosis in HALI. The current study used hyperoxia to injure two models, one HALI mouse model and one MLE-12 cell injury model. We found that WED treatment attenuated HALI by decreasing the lung injury score and lung wet/dry (W/D) weight ratio and alleviating pathomorphological changes. Then, the inflammatory reaction and apoptosis in HALI mice and hyperoxia-mediated MLE-12 cells were inhibited by WED treatment. Moreover, WED alleviated ferroptosis with less iron accumulation and reversed expression alterations of ferroptosis markers, including MDA, GSH, GPX4, SLC7A11, FTH1, and TFR1 in hyperoxia-induced MLE-12 cells in vitro and in vivo. Nrf2-KO mice and Nrf2 inhibitor (ML385) decreased WED's ability to protect against apoptosis, inflammatory response, and ferroptosis in hyperoxia-induced MLE-12 cells. Collectively, our data highlighted the alleviatory role of WED in HALI by activating the Nrf2/HO-1 pathway.
氧中毒诱导的急性肺损伤（HALI）是氧疗的一种并发症。铁死亡是 HALI 的一个重要因素。本文旨在研究柳叶菜苷（WED）对 HALI 中铁死亡的潜在作用机制。本研究采用高氧损伤两种模型，即 HALI 小鼠模型和 MLE-12 细胞损伤模型。结果发现，WED 治疗可通过降低肺损伤评分和肺湿/干（W/D）重量比以及减轻病理形态变化来减轻 HALI。此外，WED 可抑制 HALI 小鼠和高氧介导的 MLE-12 细胞中的炎症反应和细胞凋亡。而且，WED 可减轻铁死亡，减少铁积累，并逆转铁死亡标志物的表达改变，包括 MDA、GSH、GPX4、SLC7A11、FTH1 和 TFR1，在体外和体内高氧诱导的 MLE-12 细胞中。Nrf2-KO 小鼠和 Nrf2 抑制剂（ML385）降低了 WED 在高氧诱导的 MLE-12 细胞中对抗细胞凋亡、炎症反应和铁死亡的保护作用。综上所述，我们的数据强调了 WED 通过激活 Nrf2/HO-1 通路在 HALI 中的缓解作用。
