经耳后注射炎症汤建立的新型梅尼埃病动物模型

文献信息

中文摘要

背景： 内淋巴积水（EH）长期以来被认为是梅尼埃病（MD）的主要病理特征。因此，现有的大多数MD动物模型均为EH模型，但它们无法完全反映MD的所有病理特征。此外，EH与MD之间的因果关系仍存在争议。本研究的目的是开发一种能够准确反映该疾病临床和病理生理特征的MD动物模型。
方法： 6-8周龄雄性C57BL/6J小鼠连续5周每日在右侧耳后沟中部注射炎症汤（IS）。每周采用苏木精-伊红染色评估EH。采用听性脑干反应测试和免疫荧光染色评估听觉功能变化。采用旷场实验、平衡木实验、前庭眼反射和免疫荧光染色评估前庭功能。
结果： 形态学结果显示，IS注射后2周耳蜗切片出现EH。听性脑干反应结果显示，IS注射后第2周阈值显著升高。I波振幅在注射后第1周即出现下降。免疫荧光分析显示内毛细胞突触带计数减少，螺旋神经节细胞密度降低。每次IS注射后即刻，小鼠表现出转圈行为和短暂激越，持续约10秒。IS注射后第1、2和5周，旷场实验观察到自主活动减少。前庭测试显示，IS注射后第2和5周平衡木穿越时间延长，第1、2和5周前庭眼反射增益降低。形态学结果还显示椭圆囊和半规管壶腹嵴静纤毛束密度降低。
结论： 本研究建立了一种表现出MD若干关键特征的动物模型，包括EH、听力损失和前庭功能障碍。该模型可能为研究MD的发病机制和探索潜在治疗策略提供有用的实验工具。

英文摘要

BACKGROUND: Endolymphatic hydrops (EH) has long been considered the primary pathological feature of Meniere's disease (MD). Consequently, most existing animal models of MD are EH models, yet they cannot fully reflect all the pathological features of MD. Moreover, the causal relationship between EH and MD remains controversial. The objective of this study is to develop an animal model of MD that accurately reflects the clinical and pathophysiological characteristics of the disease.
METHODS: Male C57BL/6J mice aged 6-8 weeks received daily injections of inflammatory soup (IS) at the middle of the right postauricular groove for 5 consecutive weeks. EH was assessed weekly using hematoxylin and eosin staining. Changes in auditory function were evaluated using auditory brainstem response testing and immunofluorescence staining. Vestibular function was assessed using the open-field test, balance beam test, vestibulo-ocular reflex, and immunofluorescence staining.
RESULTS: Morphological findings revealed EH in cochlear sections 2 weeks after IS injection. The auditory brainstem response results showed significantly higher thresholds by week 2 after IS injection. The I-wave amplitude decreased as early as week 1 after injection. Immunofluorescence analysis demonstrated reduced inner hair cell synaptic ribbon counts and decreased spiral ganglion cell density. Immediately after each IS injection, the mice exhibited circling behavior and transient agitation, lasting approximately 10 seconds. Decreased locomotor activity was observed in the open-field test at 1, 2, and 5 weeks after IS injection. Vestibular testing showed prolonged balance beam-crossing time at 2 and 5 weeks and reduced vestibulo-ocular reflex gain at 1, 2, and 5 weeks after IS injection. Morphological findings also revealed decreased stereocilia bundle density in the utricle and cristae of the semicircular canals.
CONCLUSIONS: This study established an animal model exhibiting several key features of MD, including EH, hearing loss, and vestibular dysfunction. This model may provide a useful experimental tool for investigating the pathogenesis of MD and exploring potential therapeutic strategies.