中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (7): 1601-1606.doi: 10.4103/1673-5374.358606

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

PTEN抑制剂双过氧化钒减轻噪音引起的听觉损伤

  

  • 出版日期:2023-07-15 发布日期:2023-01-12
  • 基金资助:
    国家自然科学基金项目(81670925,81870732,81800918,81900933);陕西省科技厅重点产业创新链社会发展领域基金项目(2021ZDLSF02-12);陕西省自然科学基金项目(2019JM-009)

PTEN inhibitor bisperoxovanadium protects against noise-induced hearing loss

Bei Fan#, Fei Lu#, Wei-Jia Du#, Jun Chen, Xiao-Gang An, Ren-Feng Wang, Wei Li, Yong-Li Song, Ding-Jun Zha*, Fu-Quan Chen*   

  1. Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China
  • Online:2023-07-15 Published:2023-01-12
  • Contact: Fu-Quan Chen, PhD, chenfq@fmmu.edu.cn; Ding-Jun Zha, PhD, zhadjun@fmmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81670925 (to FQC), 81870732 (to DJZ), 81800918 (to WL), 81900933 (to YLS); Department of Science and Technology Key Industry Innovation Chain Social Development Field Fund of Shaanxi Province, No. 2021ZDLSF02-12 (to FQC); and the Natural Science Foundation of Shaanxi Province, No. 2019JM-009 (to JC).

摘要:

作者既往研究已证实第10号染色体上缺失与张力蛋白同源的磷酸酶(phosphatase and tensin homologue deleted on chromosome ten,PTEN)可参与调控耳蜗毛细胞的存活。双过氧化钒可通过抑制PTEN表达来保护神经变性,其是否可保护噪声损伤引起的听觉障碍及其机制尚待研究。为此,实验以105 dB噪声暴露2h建立了噪音性听力损失小鼠模型,可见PTEN在Corti器中外毛细胞、内毛细胞和侧壁组织的表达增加,而以双过氧化钒腹腔注射预处理可明显降低听觉阈值以及耳蜗毛细胞和内毛细胞带的缺失。此外,噪声暴露还能降低小鼠耳蜗组织中磷酸化PI3K和磷酸化Akt水平,而双过氧化钒预处理或敲低PTEN均能上调PI3K-Akt的活性。有趣的是,双过氧化钒还能通过减少耳蜗外植体中线粒体活性氧的产生来预防H2O2诱导的毛细胞死亡。这些发现表明,双过氧化钒能减轻噪声诱导的听觉损伤和减少耳蜗毛细胞损失。

https://orcid.org/0000-0002-4625-073X (Fu-Quan Chen); https://orcid.org/0000-0002-9380-9209 (Ding-Jun Zha)

关键词: 噪声暴露, 听觉损伤, 永久性阈值偏移, 耳蜗毛细胞缺失, 内毛细胞带缺失, 双过氧化钒, PTEN, siPTEN, PI3K, Akt, 氧化应激

Abstract: Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H2O2-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants. These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss. 

Key words: acoustic trauma, Akt, oxidative stress, bisperoxovanadium, cochlear hair cells loss, inner hair cell ribbons loss, noise exposure, permanent threshold shift, phosphatase and tensin homologue deleted on chromosome ten, phosphatidylinositol 3 kinase, siPTEN