Diacetyl Increases Sensory Innervation and Substance P Production in Rat Trachea
Diacetyl Increases Sensory Innervation and Substance P Production in Rat Trachea
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DOI：
10.1177/0192623313493689
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发表时间：
2014-04-01
影响因子：
1.5
通讯作者：
Dey, Richard D.
中科院分区：
文献类型：
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作者：
Goravanahally, Madhusudan P.;Hubbs, Ann F.;Dey, Richard D.
吸入双乙酰，一种黄油调味剂，引起可能由感觉神经介导的气道反应。本研究探讨了二乙酰诱导的气管上皮感觉神经的变化。大鼠（n = 6/组）吸入0-、25-、249-或346-ppm的双乙酰6小时。暴露1天后取出气管和迷走神经节，标记P物质（SP）或蛋白基因产物9.5 （PGP9.5）。在吸入双乙酰酯14天前气管内灌注荧光微球，通过轴突转运鉴定向气道上皮突出的迷走神经节神经元。终点为气管上皮内SP和PGP9.5的神经纤维密度（NFD）及向气管内突出的SP阳性神经元。pgp9.5免疫反应性NFD在脱落的上皮灶中下降，提示气道感觉神经支配的丧失。然而，在脱落病灶附近的完整上皮中，暴露于346 ppm双乙酰基后，sp免疫反应性NFD从对照的0.01 +/- 0.002增加到0.05 +/- 0.01。在迷走神经节中，吸入346 ppm双乙酰基后，sp阳性气道神经元从对照组的3.3 +/- 3.0%增加到25.5 +/- 6.6%。因此，吸入二乙酰可增加气道上皮感觉神经的SP水平。由于SP在气道中的释放促进炎症和感觉神经的激活介导反射，神经变化可能有助于调味相关的肺部疾病的发病机制。
Inhalation of diacetyl, a butter flavoring, causes airway responses potentially mediated by sensory nerves. This study examines diacetyl-induced changes in sensory nerves of tracheal epithelium. Rats (n = 6/group) inhaled 0-, 25-, 249-, or 346-ppm diacetyl for 6 hr. Tracheas and vagal ganglia were removed 1-day postexposure and labeled for substance P (SP) or protein gene product 9.5 (PGP9.5). Vagal ganglia neurons projecting to airway epithelium were identified by axonal transport of fluorescent microspheres intratracheally instilled 14 days before diacetyl inhalation. End points were SP and PGP9.5 nerve fiber density (NFD) in tracheal epithelium and SP-positive neurons projecting to the trachea. PGP9.5-immunoreactive NFD decreased in foci with denuded epithelium, suggesting loss of airway sensory innervation. However, in the intact epithelium adjacent to denuded foci, SP-immunoreactive NFD increased from 0.01 +/- 0.002 in controls to 0.05 +/- 0.01 after exposure to 346-ppm diacetyl. In vagal ganglia, SP-positive airway neurons increased from 3.3 +/- 3.0% in controls to 25.5 +/- 6.6% after inhaling 346-ppm diacetyl. Thus, diacetyl inhalation increases SP levels in sensory nerves of airway epithelium. Because SP release in airways promotes inflammation and activation of sensory nerves mediates reflexes, neural changes may contribute to flavorings-related lung disease pathogenesis.