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变应性鼻炎对小鼠急性中耳炎进展和恢复的影响。

Effects of allergic rhinitis on the progression and recovery of acute otitis media in a mouse model.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dongguk University, Ilsan Hospital, Goyang, South Korea; Sensory Organ Research Institute, College of Medicine, Dongguk University, Gyeongju, South Korea.

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dongguk University, Ilsan Hospital, Goyang, South Korea.

出版信息

Int J Pediatr Otorhinolaryngol. 2021 Jan;140:110497. doi: 10.1016/j.ijporl.2020.110497. Epub 2020 Nov 13.

DOI:10.1016/j.ijporl.2020.110497
PMID:33218690
Abstract

OBJECTIVES

The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection.

METHODS

BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa.

RESULTS

Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups.

CONCLUSION

The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

摘要

目的

本研究旨在评估变应性鼻炎(AR)对动物模型中急性中耳炎(OM)的发展、进展和恢复的影响,并研究细菌感染的继发影响。

方法

BALB/c 小鼠分为四组:AR+OM 组、AR 组、OM 组和对照组。AR+OM 组和 AR 组用卵清蛋白(OVA)和明矾致敏,然后用 OVA 经鼻内攻击。OM 组和对照组用磷酸盐缓冲盐水(PBS)相同次数给药。在 AR 诱导后,AR+OM 组和 OM 组通过向中耳(ME)腔中手术接种非定型流感嗜血杆菌(NTHi)诱导 OM。AR 组和对照组向鼓室注射 PBS。每组再分为 6 只小鼠一组,共 4 个时间点(细菌接种后 0、2、7 和 10 天)处死小鼠,取 ME 和鼻腔黏膜进行评估。评估比较四组 OM 的发生情况和 ME 黏膜厚度。通过免疫组织化学染色评估感染 ME 黏膜中白细胞介素(IL)-1β、IL-6 和肿瘤坏死因子-α(TNF-α)的组织表达。我们还研究了鼻黏膜中的 IgE、IL-4 和 IL-5。

结果

AR+OM 组和 OM 组大多数耳朵在接种后第 2 天出现 OM。在 AR+OM 组,58.3%的耳朵在接种后第 10 天仍有 OM,而 OM 组只有 16.7%。所有组的 ME 黏膜均增厚,AR+OM 组的黏膜最厚。OM 组在接种后第 2 天达到峰值,然后减少,而 AR+OM 组的 ME 黏膜厚度持续增加至第 7 天。在 OM 组中,ME 中 IL-1β、IL-6 和 TNF-α的表达也显著增加,在接种后第 2 天达到峰值,然后逐渐减少。在 AR+OM 组中,这些蛋白的表达一直增加到第 7 天,然后减少。AR+OM 组和 AR 组 IgE 和 Th2 反应(IL-4 和 IL-5)细胞因子的表达水平高于 OM 组和对照组。

结论

变应性组对 NTHi 的炎症反应更强烈,持续时间更长,这表明 AR 影响急性细菌性 OM 的进展和随后的恢复。

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