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地塞米松对噪声性听力损失的治疗效果:小鼠全身给药与鼓室内注射对比研究

Therapeutic Effect of Dexamethasone for Noise-induced Hearing Loss: Systemic Versus Intratympanic Injection in Mice.

作者信息

Han Min Ah, Back Sang A, Kim Hong Lim, Park So Young, Yeo Sang Won, Park Shi Nae

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Otol Neurotol. 2015 Jun;36(5):755-62. doi: 10.1097/MAO.0000000000000759.

Abstract

OBJECTIVE

Dexamethasone is commonly used clinically to treat noise-induced hearing loss (NIHL) because the drug exerts multiple anti-inflammatory effects. In the present study, we investigated the post-noise therapeutic effects of dexamethasone given systemically or via intratympanic injection in the mouse.

ANIMALS

Twenty-four C57BL/6J mice were used. Eighteen experimental mice were exposed to 110 dB sound pressure level white noise and then divided into three groups: the noise, intraperitoneal dexamethasone injection (IP), and intratympanic dexamethasone injection (IT) groups.

METHODS

Dexamethasone (3 mg/kg/d) was injected intraperitoneally for five successive days in the IP group. Intratympanic injections were given on post-noise days 1 and 4 in the IT group. We compared hearing levels, the architecture of the organ of Corti (OC), and the microscopic appearance of the medial olivocochlear efferent terminals (MOC ETs) among the groups.

RESULTS

Both the IP and IT groups exhibited hearing recovery as revealed by auditory brainstem responses (ABRs), but recovery was not apparent in distortion product otoacoustic emissions (DPOAEs). OC degeneration as revealed by light microscopy was most extensive in the noise group and least extensive in the IP group. Scanning electron microscopy showed that the OC ultrastructure was better preserved in the IP than the IT group. Confocal microscopy showed that the ETs were shrunken in all noise-exposed groups as compared to the control group, but more shrunken in the dexamethasone-treated groups. Transmission electron microscopy showed that the MOC ET-outer hair cell (OHC) synapses were damaged in all noise-exposed groups, but the extent of degeneration was less in the IT than in the noise group.

CONCLUSION

Dexamethasone exerts reliable therapeutic effects when used to treat NIHL. It seems that the protective effects may differ by the routes of administration as the OCs were better preserved in the IP group and the ET-OHC synapses were more intact in the IT group.

摘要

目的

地塞米松在临床上常用于治疗噪声性听力损失(NIHL),因为该药物具有多种抗炎作用。在本研究中,我们调查了全身给药或经鼓膜内注射地塞米松对小鼠噪声后治疗效果。

动物

使用24只C57BL/6J小鼠。18只实验小鼠暴露于110分贝声压级的白噪声,然后分为三组:噪声组、腹腔注射地塞米松(IP)组和鼓膜内注射地塞米松(IT)组。

方法

IP组连续5天腹腔注射地塞米松(3毫克/千克/天)。IT组在噪声暴露后第1天和第4天进行鼓膜内注射。我们比较了各组的听力水平、柯蒂氏器(OC)结构以及内侧橄榄耳蜗传出终末(MOC ETs)的微观外观。

结果

听觉脑干反应(ABR)显示IP组和IT组均出现听力恢复,但畸变产物耳声发射(DPOAE)未显示明显恢复。光镜显示OC退变在噪声组最为广泛,在IP组最不广泛。扫描电子显微镜显示IP组OC超微结构比IT组保存更好。共聚焦显微镜显示,与对照组相比,所有噪声暴露组的ETs均萎缩,但在接受地塞米松治疗的组中萎缩更明显。透射电子显微镜显示,所有噪声暴露组的MOC ET-外毛细胞(OHC)突触均受损,但IT组退变程度低于噪声组。

结论

地塞米松用于治疗NIHL时具有可靠的治疗效果。似乎保护作用可能因给药途径而异,因为IP组的OC保存更好,IT组的ET-OHC突触更完整。

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