Laboratory of Smile Snail, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Korea.
Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Korea.
Int J Mol Sci. 2018 Sep 19;19(9):2836. doi: 10.3390/ijms19092836.
To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model.
A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs.
In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7⁻14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.
为了确定用于诊断耳毒性的小鼠模型血清中循环 microRNAs (miRNAs) 的水平和检测时间，评估了血清中的循环 miR-205，以反映耳蜗微观结构的损伤，并与肾脏损伤模型进行比较。
进行了 miRNA 血清微阵列分析，以评估卡那霉素-速尿的耳毒性作用。比较了耳毒性和正常小鼠组血清和耳蜗（血管纹、柯蒂氏器和耳蜗轴）微观结构中选定 miRNA（miR-205、miR-183 和 miR-103）水平的变化。使用急性肾损伤 (AKI) 小鼠模型来评估耳毒性药物对肾脏中 miR-205 水平的变化。
在耳毒性小鼠模型中，循环 miR-205 的血清水平在第 3 天达到峰值，并在第 7⁻14 天持续升高。此外，miR-205 在第 5 天的柯蒂氏器中高表达，在第 14 天的耳蜗轴中持续高水平表达，最后在血管纹中也有表达。AKI 小鼠的血清 miR-205 与正常组相比没有明显变化。结论：耳毒性损伤后，来自耳蜗的循环 miR-205 通过血管迁移到器官，最终在血液中发现。在使用耳毒性药物导致听力损伤的情况下，可以通过检测血液中的循环 miR-205 来确定听力损失的程度。将来，通过在使用耳毒性药物导致听力损伤之前进行简单的血液检查，就可以识别内耳损伤。
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