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昼夜节律基因的抑制促进巨噬细胞浸润于小鼠电子烟烟雾诱导的肺纤维化中。

Inhibition of Circadian Rhythm Gene Promotes Macrophage Infiltration in e‑Cigarette Aerosol-Induced Pulmonary Fibrosis in Mice.

作者信息

Dong Cuishuang, Li Bin, Liu Cong, Cui Jiajing, Li Yunhui, Liang Lirong, Song Yang, Li Xiaobo

机构信息

Beijing Key Laboratory of Environment and Aging, School of Public Health, Capital Medical University, Beijing 100069, China.

School of Energy and Environment, Southeast University, Nanjing, Jiangsu 210096, China.

出版信息

Environ Health (Wash). 2025 May 16;3(8):866-877. doi: 10.1021/envhealth.5c00031. eCollection 2025 Aug 15.

DOI:10.1021/envhealth.5c00031
PMID:40837685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12362209/
Abstract

Although electronic cigarettes (e-cigarettes) are a substitute for traditional cigarettes, increasing studies indicate that e-cigarettes are unsafe. Here, we first analyzed the constituents of e-cigarette liquid (e-liquid) and e-liquid vaping-produced aerosols (e-aerosols) by gas chromatography quadrupole time-of-flight mass spectrometry (GC/Q-TOF MS) and inductively coupled plasma-MS (ICP-MS), and our result indicated that the components of e-aerosols differed from those of e-liquid. However, there is insufficient evidence on the toxicity of e-aerosols; therefore, an animal study was conducted accordingly. Mice were exposed to e-aerosols for 30, 60, or 90 days within a whole-body exposure chamber equipped with an air quality monitor. Compared with the control, weakened lung function and fiber deposition in murine lungs were observed following e-cigarette exposure. Microcomputed tomography (Micro-CT) images suggested fibrosis-like lesions in the lungs. Mechanistically, the expression of the core circadian rhythm gene, , was significantly inhibited by e-aerosols, which is negatively correlated with interleukin-6 (IL6) expression and resulted in continuous IL6 macrophage infiltration in the lungs during both daytime and night. Eventually, the knockout of expression could completely resist e-aerosol-induced pulmonary fibrosis in mice. Our results raise concerns regarding the role of circadian rhythm in regulating pulmonary fibrosis and the potential damages of e-cigarette consumption.

摘要

尽管电子烟是传统香烟的替代品,但越来越多的研究表明电子烟并不安全。在此,我们首先通过气相色谱-四极杆飞行时间质谱(GC/Q-TOF MS)和电感耦合等离子体质谱(ICP-MS)分析了电子烟液(烟液)和烟液雾化产生的气溶胶(电子气溶胶)的成分,我们的结果表明电子气溶胶的成分与烟液不同。然而,关于电子气溶胶毒性的证据不足;因此,相应地进行了一项动物研究。在配备空气质量监测器的全身暴露舱内,将小鼠暴露于电子气溶胶中30、60或90天。与对照组相比,电子烟暴露后观察到小鼠肺功能减弱和肺内纤维沉积。微型计算机断层扫描(Micro-CT)图像显示肺部有纤维化样病变。从机制上讲,核心昼夜节律基因的表达受到电子气溶胶的显著抑制,这与白细胞介素-6(IL6)的表达呈负相关,并导致白天和夜间肺内持续有IL6巨噬细胞浸润。最终,基因敲除可以完全抵抗电子气溶胶诱导的小鼠肺纤维化。我们的研究结果引发了人们对昼夜节律在调节肺纤维化中的作用以及电子烟消费潜在危害的关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/81a2789f7e90/eh5c00031_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/e24295fadcdb/eh5c00031_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/2260c0170b29/eh5c00031_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/59d6261ff906/eh5c00031_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/e89e53b31d5d/eh5c00031_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/81a2789f7e90/eh5c00031_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/e24295fadcdb/eh5c00031_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/2260c0170b29/eh5c00031_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/59d6261ff906/eh5c00031_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/e89e53b31d5d/eh5c00031_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ff/12362209/81a2789f7e90/eh5c00031_0005.jpg

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本文引用的文献

1
Unveiling Oral Health Impacts of Vaping in African Americans through Untargeted Metabolomics and Proteomics.通过非靶向代谢组学和蛋白质组学揭示电子烟对非裔美国人口腔健康的影响
Environ Health (Wash). 2025 Apr 2;3(7):733-746. doi: 10.1021/envhealth.4c00276. eCollection 2025 Jul 18.
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Macrophages protect against sensory axon loss in peripheral neuropathy.巨噬细胞可预防周围神经病变中的感觉轴突损失。
Nature. 2025 Apr;640(8057):212-220. doi: 10.1038/s41586-024-08535-1. Epub 2025 Feb 12.
3
Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway.
巨噬细胞STING信号通过IL6-STAT3途径促进良性气道狭窄中的纤维化。
Nat Commun. 2025 Jan 3;16(1):289. doi: 10.1038/s41467-024-55170-5.
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Chemical Composition of Aerosols from the E-Cigarette Vaping of Natural and Synthetic Cannabinoids.天然和合成大麻素电子烟雾化产生的气溶胶的化学成分
Chem Res Toxicol. 2024 Dec 16;37(12):1965-1975. doi: 10.1021/acs.chemrestox.4c00326. Epub 2024 Nov 13.
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Ultrasonic Cigarettes: Chemicals and Cytotoxicity are Similar to Heated-Coil Pod-Style Electronic Cigarettes.超声香烟:化学成分和细胞毒性与加热线圈式烟弹电子烟相似。
Chem Res Toxicol. 2024 Aug 19;37(8):1329-1343. doi: 10.1021/acs.chemrestox.4c00085. Epub 2024 Jul 25.
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Spatiotemporal distribution of oxidative potential in PM and its key components across six Chinese cities.中国六个城市中细颗粒物(PM)及其关键成分氧化潜能的时空分布
J Hazard Mater. 2024 Sep 5;476:135119. doi: 10.1016/j.jhazmat.2024.135119. Epub 2024 Jul 6.
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Nicotine induces senescence in spermatogonia stem cells by disrupting homeostasis between circadian oscillation and rhythmic mitochondrial dynamics via the SIRT6/Bmal1 pathway.尼古丁通过 SIRT6/Bmal1 通路破坏昼夜节律振荡和节律性线粒体动力学之间的平衡,诱导精原干细胞衰老。
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Trends Genet. 2024 Oct;40(10):834-852. doi: 10.1016/j.tig.2024.05.006. Epub 2024 Jun 12.
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