自噬在硫酸卡那霉素慢性致聋大鼠耳蜗核神经元中的作用及机制

项目名称： 自噬在硫酸卡那霉素慢性致聋大鼠耳蜗核神经元中的作用及机制

项目编号： No.81500796

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： 范国润

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 耳聋是最为常见的健康问题之一，3-4%发展中国家的成人和儿童听力损失以及众多的发达国家的成人听力损失与氨基糖苷类抗生素有关。氨基糖苷类抗生素致聋的生化和分子机制还尚未完全清楚。我们的前期研究已证实硫酸卡那霉素对大鼠蜗神经背核神经元有损伤作用，并且在给药完后神经元中自噬小体及自噬溶酶体增多。自噬在硫酸卡那霉素慢性致聋大鼠蜗神经背核神经元中的作用及其机制尚不清楚。本研究拟在建立硫酸卡那霉素慢性致聋模型的基础上，用Rapamycin和3-Methyladenine来增强或抑制硫酸卡那霉素慢性致聋大鼠的自噬功能，然后采用透射电镜、激光共聚焦、实时定量PCR、Western Blot、siRNA干扰技术及流式细胞术等技术，在动物活体及细胞水平上探索自噬在硫酸卡那霉素慢性致聋大鼠耳蜗核中的作用及其机制，为进一步阐明氨基糖苷类抗生素致聋的机制具有现实意义，及为可能的药物治疗提供实验依据。

中文关键词： 耳蜗核；螺旋神经节；药物性聋；耳毒性；细胞凋亡

英文摘要： Hearing loss is one of the most common health problems. There are 3-4% of the hearing loss cases of adults and children in developing countries and most of the adult ones in developed countries related to aminoglycosides antibiotics. The biochemical and molecular mechanisms underlying the hearing loss due to aminoglycosides antibiotics remain obscure. Our previous study has demonstrated that kanamycin sulfate may exert damaging effect on DCN of rats, which results in the increase of autophagosomes and autolysosomes in the DCN neurons after administration. The exact roles of autophagy in the DCN of chronic hearing loss in rats induced by kanamycin sulfate as well as the mechanisms during this process are still not well understood. We aim to investigate the role and mechanism of autophagy in the DCN of chronic hearing loss in rats induced by kanamycin sulfate after the enhancement by Rapamycin or inhibition by 3-Methyladenine of autophagy in vivo and in vitro by means of TEM, confocal laser scanning microscopy, real-time PCR, Western blot, siRNA interference and flow cytometry, trying to elaborate the mechanism of hearing loss induced by aminoglycosides antibiotics and provide experimental evidence for potential drug treatment.

英文关键词： cochlear nucleus;spiral ganglion neuron;drug induced deafness;ototoxicity;cell apoptosis