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建立人工颗粒物诱导的肺部疾病模型,通过分析小鼠的病理变化和转录组谱。

Establishment of an artificial particulate matter-induced lung disease model through analyzing pathological changes and transcriptomic profiles in mice.

机构信息

Jeonbuk Department of Inhalation Research, Inhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, 30 Baekhak1-Gil, Jeongeup, Jeollabuk-Do, 56212, Republic of Korea.

Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea.

出版信息

Sci Rep. 2023 Apr 12;13(1):5955. doi: 10.1038/s41598-023-29919-9.

DOI:10.1038/s41598-023-29919-9
PMID:37045933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10097713/
Abstract

Particulate matter (PM), an environmental risk factor, is linked with health risks such as respiratory diseases. This study aimed to establish an animal model of PM-induced lung injury with artificial PM (APM) and identify the potential of APM for toxicological research. APM was generated from graphite at 600 °C and combined with ethylene. We analyzed diesel exhaust particulate (DEP) and APM compositions and compared toxicity and transcriptomic profiling in lungs according to the exposure. For the animal study, C57BL/6 male mice were intratracheally administered vehicle, DEP, or APM. DEP or APM increased relative lung weight, inflammatory cell numbers, and inflammatory protein levels compared with the vehicle control. Histological assessments showed an increase in particle-pigment alveolar macrophages and slight inflammation in the lungs of DEP and APM mice. In the only APM group, granulomatous inflammation, pulmonary fibrosis, and mucous hyperplasia were observed in the lungs of some individuals. This is the first study to compare pulmonary toxicity between DEP and APM in an animal model. Our results suggest that the APM-treated animal model may contribute to understanding the harmful effects of PM in toxicological studies showing that APM can induce various lung diseases according to different doses of APM.

摘要

颗粒物(PM)是一种环境风险因素,与呼吸道疾病等健康风险有关。本研究旨在建立一种由人工 PM(APM)诱导的肺损伤动物模型,并确定 APM 在毒理学研究中的潜力。APM 由 600°C 的石墨和乙烯生成。我们分析了柴油机排气颗粒物(DEP)和 APM 的成分,并根据暴露情况比较了肺毒性和转录组谱。在动物研究中,C57BL/6 雄性小鼠经气管内给予载体、DEP 或 APM。与载体对照组相比,DEP 或 APM 增加了肺的相对重量、炎症细胞数量和炎症蛋白水平。组织学评估显示,DEP 和 APM 组的肺泡巨噬细胞中出现了更多的颗粒-色素,肺部有轻微炎症。在仅 APM 组中,一些个体的肺部出现了肉芽肿性炎症、肺纤维化和粘液增生。这是首次在动物模型中比较 DEP 和 APM 之间的肺部毒性。我们的结果表明,APM 处理的动物模型可能有助于理解 PM 在毒理学研究中的有害影响,表明 APM 可根据 APM 的不同剂量诱导各种肺部疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/49c674b3cebf/41598_2023_29919_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/02d7b0091c79/41598_2023_29919_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/89cf44c29788/41598_2023_29919_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/ae433c2b289b/41598_2023_29919_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/49c674b3cebf/41598_2023_29919_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/02d7b0091c79/41598_2023_29919_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/89cf44c29788/41598_2023_29919_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/ae433c2b289b/41598_2023_29919_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2e/10097713/49c674b3cebf/41598_2023_29919_Fig4_HTML.jpg

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