间隙连接蛋白26（Cx26）是耳蜗基底膜相邻细胞间信息传递的重要途径，其低表达是多种感音神经性聋的共同发病机制。在正常乳鼠发育过程中，基底膜存在起源于内支持细胞的自发性钙波震荡，即细胞内钙离子浓度周期性的变化，后者不仅需要Cx26参与，而且活动依赖性地促进Cx26表达。既往研究也已证实，基底膜钙波震荡缺失将抑制支持细胞Cx26表达而诱发感音神经性聋。在前期预实验中，我们发现，飞秒激光刺激耳蜗内支持细胞，可以诱发更为强烈的基底膜钙波震荡，Cx26亦是震荡形成的关键因素。为此我们提出假说，飞秒激光诱发的基底膜钙波震荡对支持细胞Cx26低表达所致感音神经性聋具有矫治作用。本申报项目将探索飞秒激光诱发的基底膜钙波震荡的形成机制及分子生物学效应，以及飞秒激光照射对Cx26低表达小鼠聋病模型的治疗作用及其机制。项目的完成将为感音神经性聋关键发病因素的管控提供重要理论依据及技术铺垫。

Connexin 26 (Cx26) is an important protein for information transmission between adjacent cells in the basilar membrane of the cochlea. A variety of sensorineural hearing loss is directly caused by its low expression. During the development of newborn rats, the basilar membrane has spontaneous calcium oscillations, which is the periodic change of calcium level in cells originating from the inner supporting cells. This calcium oscillations not only requires Cx26 , but also promotes Cx26 expression in an activity-dependent manner. Previous studies have also shown that loss of basilar membrane calcium oscillations will inhibit the expression of Cx26 in supporting cells and then cause sensorineural hearing loss. Our preliminary experiments found the stimulation of femtosecond laser to inner supporting cells can induce intense basilar membrane calcium oscillation, and Cx26 is also a key protein in the formation of calcium oscillation. Therefore, we hypothesized that calcium oscillation in basilar membrane induced by femtosecond laser has a corrective effect on sensorineural hearing loss caused by low expression of Cx26. This project will explore the formation mechanism and molecular biological effects of calcium oscillation in basilar membrane induced by femtosecond laser, and the therapeutic effect and mechanism of stimulation by femtosecond laser for low Cx26 expression mouse model. This project will provide potentially important theoretical basis and technical preparation for dealing with the key pathogenic factors of sensorineural hearing loss.