缝隙连接蛋白26在老年性耳聋中的表达及其甲基化作用机制研究

项目名称： 缝隙连接蛋白26在老年性耳聋中的表达及其甲基化作用机制研究

项目编号： No.81500795

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吴瑕

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 缝隙连接蛋白26在维持内耳稳态及正常听力中发挥着重要作用，近期研究发现拟老化大鼠内耳中Cx26甲基化率升高而其表达水平降低，然而其在老年性耳聋中的机制尚不明确。本课题在通过拟老化大鼠模型在体水平探索拟老化大鼠内耳中Cx26的表达是否依赖于Cx26基因启动子区域甲基化程度，并通过RNA干扰及腺病毒载体基因转染技术对Cx26在耳蜗内的表达进行调控，进一步动态分析该生物作用是否影响细胞内氧化应激产物的改变从而加速线粒体损伤，以期阐明Cx26参与内耳老化及其可能调节机制，为明确AHL发病机制提供新的思路。

中文关键词： 动物模型；缝隙连接蛋白；甲基化；老化；老年性耳聋

英文摘要： Connexin 26 (Cx26), one of the major protein subunits forming gap junctions, is important in maintaining homeostasis in the inner ear and normal hearing. Recent research presented that the expression of Cx26 decreased in mimetic inner ears, and the DNA methylation status of Cx26 gene was higher than control group. However, it's not clear how Cx26 contributes to age-related hearing loss (AHL). In this research, we aim to study the relationship between the expresstion of Cx26 and its DNA methyation in the inner ear of the mimetic aging rat model. Furthermore, we target interfering Cx26 expression by RNA interfering technology and gene transfection to discuss the effects of Cx26 to oxidative stress products and mitochondrial dysfunction in vivo. The study aims to explore the potential mechanisms of Cx26 on aging, which is profitable for us to have more knowledge of AHL.

英文关键词： animal model;connexin;methylation;aging;presbycusis