MacArthur Carol J, Hefeneider Steven H, Kempton J Beth, Trune Dennis R
Department of Otolaryngology & Oregon Hearing Research Center, Oregon Health & Science University, and the Department of Immunology, Veteran's Affairs Medical Center, Portland, Oregon, USA.
Laryngoscope. 2006 Jul;116(7):1071-9. doi: 10.1097/01.mlg.0000224527.41288.c4.
OBJECTIVES/HYPOTHESIS: Chronic otitis media is a significant clinical problem. Understanding the mechanisms of chronic otitis media is critical for its control. However, little is known of these processes as a result of lack of animal models of spontaneous otitis media. The C3H/HeJ mouse has a single amino acid substitution in its toll-like receptor 4 (TLR4), making it insensitive to endotoxin. As a result, these mice cannot clear Gram-negative bacteria. The chronically inflamed middle ear in this animal provides us the opportunity to study spontaneous chronic otitis media.
Otoscopy and auditory brain response (ABR) evaluation of C3H/HeJ mice at 3, 5, 7, 9, and 11 months were carried out under sedation. At 12 months of age, mice were killed and histologic analysis of the middle ear, inner ear, and eustachian tube was carried out.
Tympanic membrane visualization and ABR thresholds in 7- to 8-month-old C3H/HeJ mice showed that approximately half developed middle and inner ear disease spontaneously. The significant elevation of thresholds suggested a sensorineural component in addition to the conductive loss. Middle and inner ear histology showed some degree of middle and inner ear inflammation in half the mice, paralleling the ABR data.
The histopathologic changes reported here in the C3H/HeJ mouse model of chronic otitis media have been reported in human chronic otitis media. This spontaneous model of chronic otitis media will be valuable for the characterization of middle and inner ear inflammatory disease processes that are induced by middle ear infections.
目的/假设：慢性中耳炎是一个重要的临床问题。了解慢性中耳炎的发病机制对于控制该病至关重要。然而，由于缺乏自发性中耳炎的动物模型，对这些过程了解甚少。C3H/HeJ小鼠的Toll样受体4（TLR4）存在单个氨基酸替换，使其对内毒素不敏感。因此，这些小鼠无法清除革兰氏阴性菌。该动物慢性炎症的中耳为我们提供了研究自发性慢性中耳炎的机会。
在镇静状态下对3、5、7、9和11月龄的C3H/HeJ小鼠进行耳镜检查和听性脑干反应（ABR）评估。在12月龄时，处死小鼠并对中耳、内耳和咽鼓管进行组织学分析。
7至8月龄C3H/HeJ小鼠的鼓膜可视化和ABR阈值显示，约一半小鼠自发出现中耳和内耳疾病。阈值的显著升高表明除传导性听力损失外还存在感音神经性成分。中耳和内耳组织学显示，一半小鼠存在一定程度的中耳和内耳炎症，与ABR数据一致。
慢性中耳炎C3H/HeJ小鼠模型中报道的组织病理学变化在人类慢性中耳炎中也有报道。这种慢性中耳炎的自发模型对于表征由中耳感染引起的中耳和内耳炎症性疾病过程将具有重要价值。
