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依那西普(etanercept)抑制 TNF-α 可通过改善体内耳蜗血流预防噪声性听力损失。

TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo.

机构信息

Walter Brendel Centre of Experimental Medicine (WBex), University of Munich (LMU), Germany.

出版信息

Int J Audiol. 2013 Aug;52(8):545-52. doi: 10.3109/14992027.2013.790564. Epub 2013 Jun 20.

Abstract

OBJECTIVE

Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-α 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-α 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-α inhibitor in contrast to a significant threshold raising in controls.

CONCLUSIONS

TNF-α inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.

摘要

目的

暴露于强噪声会损害耳蜗微循环,并导致噪声性听力损失(NIHL)。已经表明 TNF-α 信号在 NIHL 中被激活,并控制调节耳蜗微循环的螺旋蜗轴动脉收缩。本实验研究旨在分析 TNF-α 抑制剂依那西普对体内 NIHL 耳蜗微循环和听力阈值变化的影响。

设计

在使用 ABR 评估正常听力后,在豚鼠的双耳上施加 106dB SPL 的强噪声(30 分钟)。在强噪声暴露后,依那西普通过全身给药,而对照动物接受生理盐水。在手术暴露耳蜗进行微循环分析后,进行纹状毛细管的活体荧光显微镜检查。ABR 测量值来自对侧耳朵。

研究样本

豚鼠(每组 6 只)。

结果

与对照组相比,依那西普治疗组的纹状毛细管段耳蜗血流明显增加。此外,与对照组中显著的阈值升高相比,接受 TNF-α 抑制剂的动物的听力阈值得到了保留。

结论

使用依那西普抑制 TNF-α 可改善强噪声暴露后的耳蜗微循环并保护听力水平,这似乎是治疗人类 NIHL 的一种有前途的治疗策略。

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