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Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers

机译:T型钙通道阻滞剂对成年C57BL / 6J小鼠耳蜗毛细胞的保护

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The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6-8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24-26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24-26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected.
机译:本研究的目的是使用C57BL / 6J小鼠模型研究T型钙通道阻滞剂对老年性耳聋的保护作用。使用逆转录-定量聚合酶链反应评估6-8周龄C57BL / 6J小鼠耳蜗中三个T型钙通道受体亚单位的表达。结果证实了三个亚基在耳蜗中表达。此外,在用米贝拉地尔,贝尼地平或生理盐水治疗4周的小鼠中,研究了T型钙通道阻滞剂保护24-26周龄C57BL / 6J小鼠的耳蜗毛细胞的能力。使用听觉脑干录音(ABR)检测到听力阈值的差异,而使用失真产物耳声发射(DPOAE)测试测量幅度的差异。 ABR测试结果表明,与生理盐水治疗组相比,米贝拉地尔治疗组和贝尼地平治疗组的听力阈值在24 kHz时明显降低。在F2频率为11.3和13.4 kHz的情况下,米贝拉地尔治疗组的DPOAE振幅与盐水治疗组相比有所增加。此外,在13.4 kHz的F2频率下,贝尼地平治疗组的DPOAE振幅比盐水治疗组的DPOAE振幅增加。米贝拉地尔治疗组外毛细胞(OHCs)的丢失不明显。然而,内部毛细胞(IHC)的立体纤毛却杂乱无章。总之,这些结果表明,连续4周施用T型钙通道阻滞剂可能会改善24-26周龄的C57BL / 6J小鼠在24 kHz时的听力。给予T型钙通道阻滞剂可明显改变C57BL / 6J小鼠OHC的功能和形态。但是,IHC不受影响。

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