Tian Shuangshuang, Liu Weihao, Liu Benli, Ye Fanchao, Xu Zhenjie, Wan Qianqian, Li Yi, Zhang Xiaoxing
Hubei Engineering Research Center for Safety Monitoring of New Energy and Power Grid Equipment, Hubei University of Technology, Wuhan 430068, China.
School of Life Sciences, Westlake University, Hangzhou, China.
Sci Total Environ. 2024 Mar 15;916:170271. doi: 10.1016/j.scitotenv.2024.170271. Epub 2024 Jan 22.
The global warming and other environmental problems caused by SF emissions can be reduced due to the widespread use of eco-friendly insulating gas, perfluoropentanone (CFO). However, there is an exposure risk to populations in areas near CFO equipment, so it is important to clarify its biosafety and pathogenesis before large-scale application. In this paper, histopathology, transcriptomics, 4D-DIA proteomics, and LC-MS metabolomics of rats exposed to 2000 ppm and 6000 ppm CFO are analyzed to reveal the mechanisms of toxicity and health risks. Histopathological shows that inflammatory cell infiltration, epithelial cell hyperplasia, and alveolar atrophy accompanied by alveolar wall thickening are present in both low-dose and high-dose groups. Analysis of transcriptomic and 4D-DIA proteomic show that Cell cycle and DNA replication can be activated by both 2000 ppm and 6000 ppm CFO to induce cell proliferation. In addition, it also leads to the activation of pathways such as Antigen processing and presentation, Cell adhesion molecules and Complement and coagulation cascades, T cell receptor signal path, Th1 and T cell receptor signal path, Th1 and Th2 cell differentiation, complement and coagulation cascades. Finally, LC-MS metabolomics analysis confirms that the metabolic pathways associated with glycerophospholipids, arachidonic acid, and linoleic acid are disrupted and become more severe with increasing doses. The mechanism of lung toxicity caused by CFO is systematically expounded based on the multi-omics analysis and provided biosafety references for further promotion and application of CFO.
由于环保型绝缘气体全氟戊酮（CFO）的广泛使用，由六氟化硫排放引起的全球变暖和其他环境问题得以减少。然而，CFO设备附近地区的人群存在接触风险，因此在大规模应用之前明确其生物安全性和发病机制很重要。本文分析了暴露于2000 ppm和6000 ppm CFO的大鼠的组织病理学、转录组学、4D-DIA蛋白质组学和LC-MS代谢组学，以揭示其毒性机制和健康风险。组织病理学显示，低剂量组和高剂量组均存在炎性细胞浸润、上皮细胞增生以及伴有肺泡壁增厚的肺泡萎缩。转录组学和4D-DIA蛋白质组学分析表明，2000 ppm和6000 ppm的CFO均可激活细胞周期和DNA复制以诱导细胞增殖。此外，它还导致抗原加工与呈递、细胞黏附分子、补体和凝血级联反应、T细胞受体信号通路、Th1和T细胞受体信号通路、Th1和Th2细胞分化、补体和凝血级联反应等途径的激活。最后，LC-MS代谢组学分析证实，与甘油磷脂、花生四烯酸和亚油酸相关的代谢途径受到破坏，且随着剂量增加而变得更加严重。基于多组学分析系统地阐述了CFO引起肺毒性的机制，并为CFO的进一步推广应用提供了生物安全性参考。
