Acute pulmonary effects of aerosolized nicotine
Acute pulmonary effects of aerosolized nicotine
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DOI：
10.1152/ajplung.00564.2017
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发表时间：
2019-01-01
影响因子：
4.9
通讯作者：
Ahmad, Aftab
中科院分区：
文献类型：
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作者：
Ahmad, Shama;Zafar, Iram;Ahmad, Aftab
尼古丁是烟草和电子烟中极易上瘾的主要成分，很容易被血液吸收。含有尼古丁的电子烟被宣传为一种安全的香烟替代品。然而，吸入尼古丁的单独影响在很大程度上是未知的。在这里，我们报告了一种新的大鼠雾化尼古丁模型，其颗粒大小（类似于1 μ m）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、肺干湿比、高迁移率组盒1 （HMGB1）蛋白升高，肺e -钙粘蛋白降低，肺水肿和肺损伤加重。免疫组化分析显示血管充血，中性粒细胞浸润增加。尼古丁暴露大鼠肺髓过氧化物酶mRNA和蛋白升高。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。尼古丁吸入动物的肺显示IL-1A和CXCL1 mRNA水平升高。IL-1 α蛋白也有所增加。在体外气液界面培养的气道上皮细胞中，尼古丁处理后HMGB1的释放呈剂量依赖性增加。暴露于尼古丁的空气-液体培养也导致了剂量依赖的屏障丧失，这是通过上皮电阻和e-钙粘蛋白表达的减少来测量的。尼古丁还引起上皮细胞死亡的剂量依赖性增加和caspase-3/7活性的增加。这些结果表明，电子烟的尼古丁含量可能对肺部和全身产生不利影响。
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 (similar to 1 mu m) 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-1 alpha 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.