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急性吸食电子烟会导致金黄仓鼠产生炎症反应的转录组变化。

Acute vaping in a golden Syrian hamster causes inflammatory response transcriptomic changes.

机构信息

Department of Pediatrics, University of Iowa, Iowa City, Iowa.

Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2022 Nov 1;323(5):L525-L535. doi: 10.1152/ajplung.00162.2022. Epub 2022 Aug 30.

Abstract

E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of subacute and chronic e-cigarette vaping exposure have shown many proinflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration of the animal or virus. Using a 2-day, whole body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung, and nasal histopathology, and gene expression in the nasopharynx and lung through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant ( < 0.05), post hoc Tukey-Kramer and Dunn's tests, respectively, were performed to make pairwise comparisons between groups. In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in gene expression associated with type 1 inflammation ( and ), fibrosis [transforming growth factor-β ()], nicotine-independent increase oxidative stress response (), and a nicotine-independent decrease in vasculogenesis/angiogenesis (VEGF-A). In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway [angiotensin-converting enzyme (), ], coagulation (, ), extracellular matrix remodeling (, ), type 1 inflammation (, , and ), fibrosis ( and ), oxidative stress response (), neutrophil extracellular traps release (), and vasculogenesis and angiogenesis () were identified. To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cigarette vaping. In addition, this is the first report that e-cigarette vaping with nicotine can increase gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation of mRNAs in the respiratory tract from pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, neutrophil extracellular trap release (NETosis), vasculogenesis, and angiogenesis.

摘要

电子烟吸食是尼古丁摄入的一个主要方面,尤其是在儿童和青少年中。尽管电子烟被宣传为一种比吸烟更安全的替代品,但在啮齿动物和大鼠的亚急性和慢性电子烟吸食暴露模型中,呼吸道出现了许多促炎变化。在金黄仓鼠中尚未证明急性电子烟吸食暴露的情况,而金黄仓鼠是一种易于获得的小型动物模型,具有独特的优势,即无需对动物或病毒进行遗传改变即可感染和传播呼吸道病毒,包括 SARS-CoV-2。使用金黄仓鼠的 2 天全身电子烟暴露方案,我们评估了血清可替宁、支气管肺泡灌洗细胞、肺和鼻组织病理学,以及通过逆转录定量聚合酶链反应 (RT-qPCR) 检测鼻和肺中的基因表达。根据是否存在非正态性或异常值,通过方差分析或 Kruskal-Wallis 检验进行统计分析。对于具有统计学意义的检验(<0.05),分别进行事后 Tukey-Kramer 和 Dunn 检验,以在组间进行成对比较。在鼻组织中,RT-qPCR 分析显示,与 1 型炎症(和)、纤维化[转化生长因子-β(])相关的基因表达呈尼古丁依赖性增加,氧化应激反应呈尼古丁非依赖性增加(),血管生成/血管生成呈尼古丁非依赖性减少(VEGF-A)。在肺部,鉴定出与肾素-血管紧张素途径相关的基因表达增加[血管紧张素转换酶()]、凝血(、)、细胞外基质重塑(、)、1 型炎症(、、和)、纤维化(和)、氧化应激反应()、中性粒细胞胞外诱捕网释放()以及血管生成和血管生成(),这些变化均依赖于尼古丁。据我们所知,这是首次证明叙利亚仓鼠是电子烟吸食的可行模型。此外,这是首次报道电子烟吸食尼古丁会增加肺部的基因表达。我们的结果表明,即使是急性暴露于电子烟也会导致呼吸道中涉及肾素-血管紧张素系统、凝血、细胞外基质重塑、1 型炎症、纤维化、氧化应激反应、中性粒细胞胞外诱捕网释放(NETosis)、血管生成和血管生成的基因的显著上调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6472/9602905/cd593670198a/l-00162-2022r01.jpg

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