基因沉默介导的肿瘤坏死因子α阻断对噪声性听力损失影响的新见解
New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss.
作者信息
Rodrigues Janaína C, Bachi André L L, Silva Gleiciele A V, Rossi Marcelo, do Amaral Jonatas B, Lezirovitz Karina, de Brito Rubens
机构信息
Clinical Hospital, Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of São Paulo (USP), São Paulo 05403-000, Brazil.
Laboratory of Otolaryngology (LIM32), School of Medicine, University of São Paulo (USP), São Paulo 05403-000, Brazil.
出版信息
Int J Mol Sci. 2020 Apr 13;21(8):2692. doi: 10.3390/ijms21082692.
UNLABELLED
Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of gene silencing on the expression profile related to the TNFα metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied.
METHODS
Single ears of Wistar rats were pretreated with small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNFα metabolic pathway in the ears submitted or not to gene silencing.
RESULTS
Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears.
CONCLUSION
Our results allow us to suggest that the blockade of TNFα by gene silencing was useful to prevent noise-induced hearing loss.
未标记
噪声暴露是后天性感音神经性听力损失的第二大常见原因，我们观察到肿瘤坏死因子α（TNFα）在此过程中起作用。此前尚未研究基因沉默对噪声性听力损失实验模型中与TNFα代谢途径相关的表达谱的影响。
方法
在Wistar大鼠单耳暴露于白噪声（120 dBSPL，持续三小时）前24小时，通过鼓膜给药对其进行小干扰RNA（siRNA）预处理。噪声暴露24小时后，我们分析了听觉脑干反应短声中I、II、III和IV波的电生理阈值和振幅。此外，对进行或未进行基因沉默的耳朵进行qRT-PCR，以评估TNFα代谢途径。
结果
与未处理的耳朵相比，进行基因沉默的耳朵电生理阈值和波幅得以保留。在处理过的耳朵中发现抗凋亡基因表达增加，促凋亡基因表达减少。
结论
我们的结果表明，通过基因沉默阻断TNFα有助于预防噪声性听力损失。
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