Novaleski Carolyn K, Kimball Emily E, Mizuta Masanobu, Rousseau Bernard
Department of Hearing and Speech Sciences, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA.
Department of Otolaryngology, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA.
Tissue Cell. 2016 Oct;48(5):407-16. doi: 10.1016/j.tice.2016.08.007. Epub 2016 Aug 24.
Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases.
临床嗓音障碍给患者带来了与沟通相关的重大挑战。本研究的目的是量化声带上皮细胞中凋亡率和肿瘤坏死因子-α(TNF-α)信号,以应对振动时间剂量和周期剂量的增加。20只新西兰白色种兔被随机分为三组,分别接受不同时间剂量的振动暴露(30、60、120分钟)或对照组(声带内收和外展120分钟)。根据平均基频推断声带振动的估计周期剂量。对喉组织标本进行凋亡以及TNF-α基因转录和蛋白水平的评估。结果显示,与对照组相比,振动120分钟后末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色显著更高。透射电子显微镜(TEM)显示时间剂量对上皮细胞核平均面积无显著影响。振动暴露的推断周期剂量与实验时间剂量条件密切相关,尽管未观察到与TUNEL染色或上皮细胞核平均面积有显著相关性。TUNEL染色与TNF-α蛋白表达呈正相关。我们的研究结果表明,在模态强度发声120分钟后,声带上皮可诱导凋亡。相比之下,较短时间的振动暴露不会导致凋亡信号。然而,使用TEM未观察到凋亡的形态学特征。未来有必要开展研究,以探讨异常凋亡在声带疾病中的作用。