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柴油机废气暴露小鼠肺部的肺泡组织破坏和蛋白瓜氨酸化。

Lung alveolar tissue destruction and protein citrullination in diesel exhaust-exposed mouse lungs.

机构信息

State Research Institute Center for Innovative Medicine, Vilnius, Lithuania.

Department of Environmental Technologies, Kaunas University of Technology, Kaunas, Lithuania.

出版信息

Basic Clin Pharmacol Toxicol. 2019 Aug;125(2):166-177. doi: 10.1111/bcpt.13213. Epub 2019 Apr 2.

DOI:10.1111/bcpt.13213
PMID:30801928
Abstract

Humanity faces an increasing impact of air pollution worldwide, including threats to human health. Air pollutants prompt and promote chronic inflammation, tumourigenesis, autoimmune and other destructive processes in the human body. Post-translational modification of proteins, for example citrullination, results from damaging attacks of pollutants, including smoking, air pollution and others, rendering host tissues immunogenic. Citrullinated proteins and citrullinating enzymes, deiminases, are more prevalent in patients with COPD and correlate with ongoing inflammation and oxidative stress. In this study, we installed an in-house-designed diesel exhaust delivery and cannabidiol vaporization system where mice were exposed to relevant, urban traffic-related levels of diesel exhaust for 14 days and assessed integrity of alveolar tissue, gene expression shifts and changes in protein content in the lungs and other tissues of exposed mice. Systemic presence of modified proteins was also tested. The protective effect of phytocannabinoids was investigated as well. Data obtained in our study show subacute effects of diesel exhaust on mouse lung integrity and protein content. Emphysematous changes are documented in exposed mouse lungs. In parallel, increased levels of citrulline were detected in the alveolar lung tissue and peripheral blood of exposed mice. Pre-treatment with vaporized cannabidiol ameliorated some damaging effects. Results reported hereby provide new insights into subacute lung tissue changes that follow diesel exhaust exposure and suggest possible dietary and/or other therapeutic interventions for maintaining lung health and healthy ageing.

摘要

人类正面临着全球范围内日益严重的空气污染的影响,包括对人类健康的威胁。空气污染物会引发和促进人体的慢性炎症、肿瘤发生、自身免疫和其他破坏性过程。例如,蛋白质的翻译后修饰(例如瓜氨酸化)是由污染物(包括吸烟、空气污染等)的破坏性攻击引起的,使宿主组织具有免疫原性。瓜氨酸化蛋白和瓜氨酸化酶(脱氨酶)在 COPD 患者中更为常见,与持续的炎症和氧化应激相关。在这项研究中,我们安装了一个内部设计的柴油废气输送和大麻二酚蒸发系统,让老鼠暴露在与城市交通相关的柴油废气水平下 14 天,并评估暴露老鼠的肺泡组织完整性、基因表达变化以及肺部和其他组织中的蛋白质含量变化。还测试了系统中存在的修饰蛋白。还研究了植物大麻素的保护作用。我们的研究结果显示,亚急性柴油废气对老鼠肺部完整性和蛋白质含量有影响。暴露的老鼠肺部有肺气肿变化。同时,在暴露老鼠的肺泡组织和外周血液中检测到瓜氨酸水平升高。雾化大麻二酚预处理可以改善一些损伤作用。本报告的结果提供了对亚急性肺组织变化的新认识,这些变化是由于暴露于柴油废气引起的,并为维持肺健康和健康衰老提供了可能的饮食和/或其他治疗干预措施。

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