Li Juan, Wei Huai, Wang Ning, Chen Jing, Zhang Ying, An Zhen, Song Jie, Niu Tianqi, Wu Weidong
International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China.
Biol Trace Elem Res. 2025 Jun;203(6):3132-3142. doi: 10.1007/s12011-024-04386-z. Epub 2024 Oct 7.
In recent years, the concentration of PM in China has decreased, while the concentration of ozone remains rising. Exposure to ozone contributes to respiratory illnesses; however, little is known about the underlying molecular mechanisms. The present study established an ozone-induced lung injury mice model to investigate potential molecular biomarkers and toxic mechanisms. Collected and analyzed the ozone pollution data in Xinxiang city from 2015 to 2022. At the same time, 24 male C57BL/6 mice were randomly assigned to control group and ozone exposure group. The ozone exposure concentration is 1 ppm, with 4 h of daily exposure for 33 consecutive days. HE staining was used to assess lung histological alterations and lung injury. High-throughput sequencing performed on the lung tissues of mice was used to analyze the differential expressed genes and signal transduction pathways. Xinxiang city is suffering from ozone pollution, especially in summer. HE staining showed that the ozone exposure could induce obvious inflammatory cell infiltration, alveolar wall thickening, or fracture. Transcriptome data revealed that there is a 145 differentially expressed genes between two groups and the genes enriched in PPAR signaling pathway, ferroptosis. The pivotal genes in the PPAR pathway including Adipoq, Lpl, Pck1, and Plin1 expression were significantly reduced. Additionally, the expression of Acsl6 and Scl7a11, which are close to PPAR pathway and ferroptosis has decreased. Ozone exposure could disrupt the lipid metabolism balance via downregulating lipid peroxidation-related genes through the PPAR signaling pathway, which further induced lung cell ferroptosis and aggravated lung injury in mice.
近年来，中国细颗粒物（PM）浓度有所下降，而臭氧浓度仍在上升。接触臭氧会导致呼吸道疾病；然而，其潜在的分子机制却鲜为人知。本研究建立了臭氧诱导的肺损伤小鼠模型，以探究潜在的分子生物标志物和毒性机制。收集并分析了2015年至2022年新乡市的臭氧污染数据。同时，将24只雄性C57BL/6小鼠随机分为对照组和臭氧暴露组。臭氧暴露浓度为1 ppm，每天暴露4小时，连续暴露33天。采用苏木精-伊红（HE）染色评估肺组织学改变和肺损伤情况。对小鼠肺组织进行高通量测序，以分析差异表达基因和信号转导通路。新乡市正遭受臭氧污染，尤其是在夏季。HE染色显示，臭氧暴露可诱导明显的炎性细胞浸润、肺泡壁增厚或断裂。转录组数据显示，两组之间有145个差异表达基因，这些基因在过氧化物酶体增殖物激活受体（PPAR）信号通路、铁死亡中富集。PPAR通路中的关键基因，包括脂联素（Adipoq）、脂蛋白脂肪酶（Lpl）、磷酸烯醇式丙酮酸羧激酶1（Pck1）和脂滴包被蛋白1（Plin1）的表达显著降低。此外，与PPAR通路和铁死亡相关的长链脂酰辅酶A合成酶6（Acsl6）和溶质载体家族7成员11（Scl7a11）的表达也有所下降。臭氧暴露可通过PPAR信号通路下调脂质过氧化相关基因，从而破坏脂质代谢平衡，进而诱导小鼠肺细胞铁死亡并加重肺损伤。
