Kang Li, Xiao-Qin Wang, Zhen-Liang Liao, Jun-Ya Liu, Bang-Hai Feng, Ying-Cong Ren, Ni-Nan Dai, Kun Yu, Hong Yu, Hua-Jun Chen, Hong Mei, Song Qin
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引用次数: 0
Abstract
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 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.
高氧诱导的急性肺损伤(HALI)是氧疗的一种并发症。高铁血症是造成 HALI 的一个重要因素。本文旨在研究蟛蜞菊内酯(WED)对 HALI 中铁细胞减少的潜在机制。本研究采用高氧损伤两种模型,一种是 HALI 小鼠模型,另一种是 MLE-12 细胞损伤模型。我们发现,WED 治疗可降低肺损伤评分和肺干湿重比,减轻病理形态学变化,从而减轻 HALI。WED 还能抑制 HALI 小鼠和高氧介导的 MLE-12 细胞的炎症反应和细胞凋亡。此外,WED还能缓解铁变态反应,减少铁积累,并逆转高氧诱导的MLE-12细胞体内外铁变态反应标志物的表达变化,包括MDA、GSH、GPX4、SLC7A11、FTH1和TFR1。Nrf2-KO小鼠和Nrf2抑制剂(ML385)降低了WED保护高氧诱导的MLE-12细胞免受凋亡、炎症反应和铁变态反应的能力。总之,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。
期刊介绍:
The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology.
The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field.
The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.