外周神经髓鞘再生在高原缺氧环境听觉习服中的作用及分子调控

研究表明低氧是造成高原地区迟发性听力障碍的主要原因。我们在前期工作中发现，平原移居高原人群有听力习服现象；高原听力习服与外周听觉神经髓鞘雪旺细胞损伤再生有关。但低氧环境下影响髓鞘再生的雪旺细胞表型转换机制目前尚未阐明。课题采用体外分离耳蜗神经组织块和原代雪旺细胞，以不同氧含量预处理细胞模拟高原生态，通过观察细胞表型、增殖特征和间质化能力改变，确定低氧条件下雪旺细胞重编程规律；确定Hippo/Yap、PI3K/Akt/mTORC1信号通路和EMT相关转录因子对雪旺细胞表型转换的调控机制。以大鼠平原移居高原为模型，动态观察高原听力习服规律。观察分析耳蜗外周神经组织区域雪旺细胞亚群的改变，确定雪旺细胞的极性变化和髓鞘再生与听觉习服能力的相关性。探讨低氧髓鞘再生不同阶段关键基因的表达及调控方式。期望发现能够促进听觉系统低氧适应性调控因子，为预防低氧所致的听觉损伤和外周髓鞘病变的治疗提供理论依据。

Studies show that low oxygen is the main cause of delayed hearing impairment in the plateau region.In our previous work, we found that there are an phenomenon of sound acclimatization in the migrated population from the plain to the plateau. Animal experiments have confirmed that sound acclimatizationis associated with the regeneration of the peripheral auditory nerve myelin.However, the mechanism to regulate the regeneration of the snowman in low oxygen environment has not been clarified. This project work schwann cells from auditory area of peripheral nerve as cellular model which is treated with different oxygen content mimicked the plateau low oxygen conditions. The characteristicsof schwann cell reprogramming is determined through observed the schwann cellular polarity, change of proliferation capacity and epithelial-mesenchymal transition. The regulation mechanism of Hippo/Yap, PI3K/Akt/mTORC1 signaling pathway and EMT correlation transcription factors on phenotype transformation of the schwann cell are determined. Based on the model of the rat plain moving to the plateau, the characteristics of sound acclimatization are observed dynamicallyby auditory function detection. The correlation between the polarity change of the schwann cells andremyelination in the process of sound acclimatization are evaluated through analyzed the changes of the sub-population of schwann cells in the cochlea axis and osseous spiral lamina of the cochlea. The aim of this study is focused on discovering novel regulatory factor which can lead to hypoxic adaptation in auditory system, which provides theoretical basis for preventing the hypoxia-induced hearing impairment and treating the disorders of peripheral myelin.