槲皮苷对噪声诱导神经性耳聋小鼠的保护作用

Protective Effect of Quercetin on Noise-Induced Hearing Loss in Mice

目的探讨槲皮苷(Que)对噪声诱导神经性耳聋小鼠的作用及其潜在机制。方法将成年C57BL/6小鼠随机分成对照组(Con组)、噪声暴露组(Noise组)、低剂量Que治疗组(L-Que组)、高剂量Que治疗组(H-Que组),每组10只。除Con组外其余3组均接受噪声暴露,其中L-Que组和H-Que组在噪音暴露前分别给予50 mg·kg^-1·d^-1和100 mg·kg^-1·d^-1 Que处理。检测各组在点击音和全频程刺激下的听性脑干反应(ABR)阈值;免疫荧光染色联合激光扫描共聚焦显微镜检测耳蜗内毛细胞(IHC)、外毛细胞(OHC)的改变以及3-硝基酪氨酸(3-NT)、4-羟基壬醛(4-HNE)和微管相关蛋白轻链3B(LC3B)的表达。结果与Con组比较,Noise组ABR阈值以及OHC中3-NT、4-HNE和LC3B的表达水平均显著增加(均P<0.001),对应于频率>22.4 kHz的耳蜗位置处的OHC密度显著降低(均P<0.001);与Noise组比较,L-Que组和H-Que组ABR阈值和OHC中3-NT、4-HNE和LC3B的表达水平均显著降低(均P<0.01),对应于频率>22.4 kHz的耳蜗的位置处的OHC密度显著增加(均P<0.01),且H-Que组效果更优(P<0.01)。结论Que对噪声诱导的神经性耳聋小鼠具有保护作用,其保护作用可能是通过减少耳蜗OHC氧化应激和自噬作用来实现的。

Objective To explore the effect of quercetin(Que)on noise-induced deafness in mice and its potential mechanism.Methods Forty C57BL/6 mice were randomly divided into control group(Con group),noise exposure group(Noise group),low-dose Que treatment group(L-Que group),and high-dose Que treatment group(H-Que group),with 10 mice in each group.Mice in L-Que group and H-Que group were respectively treated with 50 and 100 mg/kg/day Que before exposure to noise.Auditory brainstem response(ABR)threshold was measured under the stimulation of click and tone burst.The changes in inner hair cells(IHC)and outer hair cells(OHC)and the expression of 3-nitrotyrosine(3-NT),4-hydroxynonaldehyde(4-HNE)and microtubule-associated protein 1 light chain 3B(LC3B)were detected by immunofluorescence staining using laser scanning confocal microscope.Results Compared with Con group,ABR threshold and expression of 3-NT,4-HNE and LC3B in OHC increased but OHC density at cochlear location corresponding to frequencies>22.4 kHz decreased in Noise group(P<0.001).Compared with Noise group,ABR threshold and expression of 3-NT,4-HNE and LC3B in OHC decreased but OHC density at cochlear location corresponding to frequencies>22.4 kHz increased in both L-Que group and H-Que group(P<0.01).Moreover,the effect of high-dose Que was better than that of low-dose Que(P<0.01).Conclusion Que can protect against noise-induced deafness in mice through reducing oxidative stress and autophagy in the OHC of the cochlea.