TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo
TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo
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DOI：
10.3109/14992027.2013.790564
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发表时间：
2013-08-01
影响因子：
2.7
通讯作者：
Strieth, Sebastian
中科院分区：
文献类型：
--
作者：
Arpornchayanon, Warangkana;Canis, Martin;Strieth, Sebastian
目的：强噪声暴露可损害耳蜗微循环，引起噪声性听力损失（NIHL）。TNF-alpha信号已被证明在NIHL中被激活，并控制螺旋蜗轴动脉血管收缩，调节耳蜗微循环。本实验研究的目的是分析TNF-α抑制剂依那西普对体内NIHL耳蜗微循环和听阈偏移的影响。实验设计：豚鼠双耳分别施加106 dBSPL的强噪声（30 min），经ABR检测听力正常。在暴露于巨大噪声后全身给予依那西普，而对照动物接受盐水溶液。在手术暴露耳蜗后，进行耳蜗毛细血管的体内荧光显微镜检查，以进行微循环分析。ABR测量来自对侧耳。研究样品：豚鼠（n=6，每组）。结果：与对照组相比，依那西普治疗组动物耳蜗毛细血管段血流量显著增加。此外，接受TNF-α抑制剂的动物的听阈保持不变，而对照组的听阈显著升高。结论：使用依那西普抑制TNF-α可改善耳蜗微循环并保护噪声暴露后的听力水平，似乎是一种有前途的治疗人类NIHL的策略。
Objective: Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-alpha signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-alpha inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. Design: After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Study sample: Guinea pigs (n=6, per group). Results: Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-alpha inhibitor in contrast to a significant threshold raising in controls. Conclusions: TNF-alpha inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.