Department of Otolaryngology Head & Neck Surgery, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
Otolaryngol Head Neck Surg. 2013 Aug;149(2):301-3. doi: 10.1177/0194599813491712. Epub 2013 Jun 4.
The objective was to detect changes in cytokine expression within cochleae in a murine model of systemic inflammation, with or without aminoglycoside exposure. Four groups of mice received 1 of the following: saline only, systemic bacterial lipopolysaccharides (LPS) for 6 hours to induce endotoxemia and inflammatory responses, systemic gentamicin for 3 hours, or both treatments. After exsanguination, pooled cochleae (4/group) were processed for enzyme-linked immunosorbent assay (ELISA) for 16 cytokines. Gentamicin alone did not change cochlear cytokine levels, while LPS (± gentamicin) substantially elevated cochlear expression of several cytokines, particularly interleukin-1α, interleukin-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES. Since cytokines increase blood-brain barrier permeability, we hypothesize that cytokine-enhanced permeability of the blood-labyrinth barrier (BLB) could potentiate aminoglycoside-induced ototoxicity. This pilot study demonstrated the feasibility of detecting cytokine expression in murine cochleae using ELISA and facilitates future studies investigating BLB permeability in animal models of systemic inflammation.
目的是检测系统性炎症模型中，伴或不伴氨基糖苷类药物暴露的情况下，耳蜗内细胞因子表达的变化。四组小鼠分别接受以下处理：仅给予生理盐水、6 小时内给予全身细菌脂多糖（LPS）以诱导内毒素血症和炎症反应、3 小时内给予全身庆大霉素、或两种处理都给予。放血后，将（每组 4 只） pooled cochleae 进行酶联免疫吸附试验（ELISA）检测 16 种细胞因子。单独使用庆大霉素不会改变耳蜗细胞因子水平，而 LPS（± 庆大霉素）则显著增加了几种细胞因子在耳蜗中的表达，特别是白细胞介素-1α、白细胞介素-6、单核细胞趋化蛋白-1、巨噬细胞炎症蛋白-1α 和 RANTES。由于细胞因子增加血脑屏障通透性，我们假设细胞因子增强血迷路屏障（BLB）的通透性可能会增强氨基糖苷类药物引起的耳毒性。这项初步研究证明了使用 ELISA 检测小鼠耳蜗内细胞因子表达的可行性，并为未来研究系统性炎症动物模型中 BLB 通透性提供了便利。
