线粒体去乙酰化蛋白SIRT3在噪声诱导隐匿性听力损失中的作用

Role of mitochondrial deacetylated protein SIRT3 on the cochlea of noise-induced hidden hearing loss

目的探讨线粒体去乙酰化蛋白(sirtuin-3,SIRT3)在噪声性隐性听力损失(noise-induced hidden hearing loss,NIHHL)中的作用。方法将注射过SIRT3抑制剂[3-(1H-1,2,3-triazol-4-yl)pyridine,3-TYP]与未经处理的C57BL/6J小鼠分别于100 dB白噪声下暴露2 h,并在噪声暴露(noise exposure,NE)后1 d和14 d进行测听。利用免疫荧光染色观察内毛细胞(inner hair cell,IHCs)带状突触(ribbon synapses,RS)的变化。冰冻切片下,4-羟基壬烯醛(4-hydroxynonenal,4-HNE)染色观察耳蜗内活性氧(reactive oxygen species,ROS)的累积。结果与对照组相比,噪声组及3-TYP组小鼠均在噪声后出现短暂性听力阈值的升高,ROS的累积及带状突触的丢失。与噪声组小鼠相比,3-TYP组小鼠在噪声后第14天听力未恢复正常,带状突触丢失明显,且伴有ROS的显著累积。结论NE诱发了内耳的氧化应激反应,SIRT3可能通过抵抗氧化应激作用来保护耳蜗带状突触及听功能。

Objective To investigate the role of mitochondrial deacetylation protein sirtuin-3(SIRT3)in noise-induced hidden hearing loss(NIHHL).Methods Injected SIRT3 inhibitor[3-(1H-1,2,3-triazol-4-yl)pyridine,3-TYP]and untreated C57BL/6J mice were exposed to 100 dB white noise for 2 hours and hearing examination was performed within 24 h or fourteen days after noise exposure(NE).The changes of ribbon synapses(RS)of inner hair cells(IHCs)were observed by immunofluorescence staining.Via the frozen section,4-hydroxynonenal(4HNE)staining was used to observe the accumulation of reactive oxygen species(ROS)in the cochlea.Results Compared with the control group,the NE group and 3-TYP group showed a temporary threshold shift,ROS accumulation and loss of ribbon synapses after NE.Compared with the NE group,the threshold of mice in 3-TYP group did not return to normal level 2 weeks after NE.We also found an obvious loss of ribbon synapses and the accumulation of ROS.Conclusion NE causes oxidative stress in the inner ear,and SIRT3 may protect auditory system function by resisting oxidative stress.