二甲基亚砜对耳蜗传出功能和外毛细胞运动性的浓度依赖性效应

文献信息

中文摘要

背景： 二甲基亚砜（DMSO）在听觉和前庭药理学中广泛用作溶剂，但其对耳蜗功能的直接影响尚未明确。我们测试了通过小鼠后半规管递送至人工外淋巴液中的DMSO，在不含活性药物的情况下，是否会改变畸变产物耳声发射（DPOAEs）和内侧橄榄耳蜗（MOC）介导的耳蜗反应。方法：单独的人工外淋巴液对MOC介导的反应或基线DPOAEs均未产生可测量的变化。相比之下，5% DMSO逐渐增加MOC介导的抑制，10% DMSO对MOC介导的抑制产生更显著的增强，而15% DMSO最初增强MOC介导的抑制，但随后导致基线DPOAEs和MOC介导的抑制均进行性丧失。平均反应曲线显示MOC介导的抑制呈浓度依赖性增加，Hill型分析得出EC50为5.29% DMSO。在较高浓度下，15% DMSO使DPOAE阈值升高约30 dB。由于含DMSO的溶液相对于人工外淋巴液明显高渗，渗透压应激可能促成了观察到的效应。结果：为测试直接耳蜗作用，我们还使用光学相干断层扫描在沙鼠离体条件下检查了外毛细胞（OHC）的电运动性。在该制备中，5% DMSO可逆地降低OHC电运动性，而无明显结构损伤。结论：这些发现表明DMSO效应取决于浓度和实验背景。尽管1% DMSO未产生可测量的效应，但直接外淋巴暴露于5%或更高浓度会改变MOC介导的反应和OHC电运动性。这些结果支持继续使用匹配的载体对照，特别是在局部内耳递送需要较高DMSO浓度时。

英文摘要

Dimethyl sulfoxide (DMSO) is widely used as a solvent in auditory and vestibular pharmacology, yet its direct effects on cochlear function are not well defined. We tested whether DMSO in artificial perilymph, delivered through the posterior semicircular canal in mice, alters distortion product otoacoustic emissions (DPOAEs) and medial olivocochlear (MOC)-mediated cochlear responses in the absence of active drug. Artificial perilymph alone produced no measurable change in either MOC-mediated responses or baseline DPOAEs. In contrast, 5% DMSO progressively increased MOC-mediated suppression, 10% DMSO produced a more marked enhancement of MOC-mediated suppression, and 15% DMSO initially enhanced MOC-mediated suppression but subsequently caused progressive loss of both baseline DPOAEs and MOC-mediated suppression. Averaged response profiles showed a concentration dependent increase in MOC-mediated suppression, and Hill-type analysis yielded an EC50 of 5.29% DMSO. At higher concentrations, 15% DMSO elevated DPOAE threshold by approximately 30 dB. Because DMSO containing solutions were markedly hyperosmotic relative to artificial perilymph, osmotic stress likely contributed to the observed effects. To test direct cochlear action, we also examined outer hair cell (OHC) electromotility ex vivo using optical coherence tomography in gerbils. In this preparation, 5% DMSO reversibly reduced OHC electromotility without obvious structural damage. These findings indicate that DMSO effects depend on centration and experimental context. Although 1% DMSO produced no measurable effect, direct perilymphatic exposure to concentrations of 5% or greater altered MOC-mediated responses and OHC electromotility. These results support the continued use of matched vehicle controls, particularly when higher DMSO concentrations are required for local inner ear delivery.