耳蜗大电导依赖性钾离子通道BK介导ROS-AMPK通路在老年性耳聋发病中的研究

Age-related hearing loss（AHL）is one of the most common disease in elder. In recent years, Downregulated potassium channels in the cochlea was widely recognized in the course of AHL. Large -conductance Ca2+-activated K+ channel (BK) plays an vital role in auditory formation and conduction of nerve signals. Dysfunction of cochlear BK is related to AHL. However, the detailed mechanic of this course is litte known. This study begin in constructing（BK+/+, BK+/-, BK-/-）mouse model, to explore the role of BK in the pathogenesis of AHL and systemtic answer the following four questions:1. Distinct morphological cochlear change in various stains（C57BL/6J，CBA/CaJ，BK+/+, BK+/-, BK-/-）mice inner ears of mice at different age（4、12、26、52 weeks）. 2. Auditory physiology in age-related manner would be operated by ABR, DPOAE in each group, while the change of potassium current in hair cells and spiral ganglion neurons would be detected by patch clamp technique in each group.3.To confirm downregulation of BK contribtes to apoptosis of hair cells and spiral ganglion neurons by ROS-AMPK signal pathway. Our study would provide a systematic understanding of the role of BK in AHL, which help us to intervene the early development of AHL.

老年性耳聋是耳鼻咽喉科常见的疾病之一，耳蜗钾离子通道数量及功能减退与老年性耳聋发病存在相关性，大钙依赖性钾通道(large-conductance Ca2+-activated K+ channel, BK)在听觉形成及神经信号的传导起必要作用，但BK在老年性耳聋作用尚未阐明。本研究拟通过构建BK+/+, BK+/-, BK-/-小鼠，探究BK在老年性耳聋的发病过程中作用，1.比较（C57BL/6J，CBA/CaJ，BK+/+, BK+/-, BK-/-）小鼠在（4、12、26、52）周耳蜗BK时空表达及耳蜗形态差异；2.比较各组小鼠听阈、耳蜗电位等年龄相关性听觉生理差异，检测各组毛细胞及螺旋神经元BK瞬时外向钾电流的年龄相关性变化；3.在体内、体外验证BK通过ROS-AMPK信号通路调控毛细胞、螺旋神经元凋亡。本研究为BK在老年性耳聋作用提供系统认识，为老年性耳聋早期干预提供新思路。

老年性耳聋是耳鼻咽喉科常见的疾病之一，耳蜗钾离子通道数量及功能减退与老年性耳聋发病存在相关性，大钙依赖性钾通道(large-conductance Ca2+-activated K+ channel, BK)在听觉形成及神经信号的传导起必要作用，本研究通过构建BK+/+, BK+/-, BK-/-小鼠，探究BK在老年性耳聋的发病过程中具体分子生物学作用， BK-/-小鼠在（4、12、26、52）周耳蜗BK时空表达及耳蜗形态呈现过度衰老表现；发现BK-/-小鼠的听阈、耳蜗电位等年龄相关性听觉生理存在早期老龄化病变，电生理研究提示毛细胞及螺旋神经元BK瞬时外向钾电流的年龄相关性变化；在体内、体外明晰了BK通过ROS-AMPK信号通路调控毛细胞、螺旋神经元凋亡具体过程，为老年性耳聋早期干预提供新思路。