Vent J, Robinson A M, Gentry-Nielsen M J, Conley D B, Hallworth R, Leopold D A, Kern R C
Department of Biomedical Sciences, Creighton University, Omaha, NE, USA.
Laryngoscope. 2004 Aug;114(8):1383-8. doi: 10.1097/00005537-200408000-00012.
To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis.
A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke.
Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis.
Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage.
These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium.
研究烟草烟雾对嗅上皮的影响。吸烟与嗅觉减退有关；然而，其病理生理学机制尚不清楚。嗅觉由暴露于鼻腔气道的嗅觉感觉神经元（OSN）介导，这使得它们易受环境损伤和死亡的影响。因此，即使在没有明显疾病的情况下，也已证实存在凋亡性OSN死亡的基线水平。死亡的OSN由祖细胞的有丝分裂和成熟所替代，以在成年期维持足够数量的神经元。这种平衡的破坏被认为是临床嗅觉丧失的常见原因。本研究将评估烟草烟雾对嗅黏膜的影响，重点是OSN凋亡程度的变化。
使用大鼠模型评估暴露于烟草烟雾后的嗅上皮。
将大鼠单独暴露于烟草烟雾（12周）、烟雾加膳食乙醇（最后5周）或不暴露于任何物质（对照组）。使用针对活性形式的半胱天冬酶-3的抗体对嗅上皮进行免疫组织化学分析。这种形式的半胱天冬酶-3酶的阳性染色表明细胞正在经历凋亡性蛋白水解。
对照大鼠在嗅上皮中显示出低基线水平的半胱天冬酶-3活性。相比之下，烟草烟雾暴露引发了OSN凋亡程度的显著增加，这影响了神经元谱系的所有阶段。
这些结果支持以下假设：吸烟者的嗅觉丧失是由OSN死亡增加引发的，最终超过了上皮的再生能力。
