Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham , Birmingham, Alabama.
Department of Pathology, University of Alabama at Birmingham , Birmingham, Alabama.
Am J Physiol Lung Cell Mol Physiol. 2019 Jan 1;316(1):L94-L104. doi: 10.1152/ajplung.00564.2017. Epub 2018 Oct 25.
Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine-containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid protein, IgM, lung wet-to-dry weight ratio, and high-mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase mRNA and protein increased in the nicotine-exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils, and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine-inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1α protein. In in vitro air-liquid interface cultures of airway epithelial cells, there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by transepithelial electrical resistance and a decrease in E-cadherin expression. Nicotine also caused a dose-dependent increase in epithelial cell death and an increase in caspase-3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects.
尼古丁是烟草和电子烟中高度成瘾的主要成分，很容易被血液吸收。含有尼古丁的电子烟被宣传为吸烟的安全替代品。然而，吸入尼古丁的孤立效应在很大程度上尚不清楚。在这里，我们报告了一种新型的雾化尼古丁大鼠模型，其颗粒大小（~1μm）在可呼吸直径范围内。急性尼古丁吸入导致肺泡灌洗液蛋白、IgM、肺湿重/干重比和高迁移率族蛋白 B1（HMGB1）蛋白增加，肺 E-钙黏蛋白蛋白减少，从而导致肺水肿和肺损伤。免疫组织化学分析显示血管充血和中性粒细胞浸润增加。尼古丁暴露大鼠的肺髓过氧化物酶 mRNA 和蛋白增加。全血细胞计数也显示中性粒细胞、白细胞、嗜酸性粒细胞和嗜碱性粒细胞增加。动脉血气测量显示乳酸增加。吸入尼古丁的动物的肺部显示白细胞介素 1A 和 CXCL1 的 mRNA 水平增加。IL-1α 蛋白也增加。在气道上皮细胞的气液界面培养中，随着尼古丁处理，HMGB1 释放呈剂量依赖性增加。暴露于尼古丁的气液培养也导致跨上皮电阻的屏障功能呈剂量依赖性丧失，E-钙黏蛋白表达下降。尼古丁还导致上皮细胞死亡呈剂量依赖性增加，caspase-3/7 活性增加。这些结果表明，电子烟中的尼古丁含量可能对肺部和全身产生不良影响。
