促红细胞生成素衍生物对钙黏蛋白突变小鼠CDH23erl/erl的听力保护作用及机制研究

项目名称： 促红细胞生成素衍生物对钙黏蛋白突变小鼠CDH23erl/erl的听力保护作用及机制研究

项目编号： No.81500797

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： 郑体花

作者单位： 滨州医学院

项目金额： 18万元

中文摘要： 耳聋是最常见的感觉障碍性疾病之一，目前没有有效的治疗药物。本实验室鉴定的钙黏蛋白-23（CDH23）突变小鼠模型Cdh23erl/erl，出生后27天(P27)发生渐进性耳聋，P27-P90的发病时间窗使其成为试验听力保护药物的理想动物模型。我们已证明促红细胞生成素（EPO）能够减缓Cdh23erl/erl小鼠内耳毛细胞缺失并具有听力保护作用（Neuroscience. 2013 May 1;237:1-6）。但是，EPO的促红细胞生成作用使其存在致血栓形成的副作用。pHBSP是EPO的衍生物，去除了EPO的促红细胞生成作用，能够更好地发挥组织保护作用，但其在听力保护中的应用尚无报道。本课题拟利用Cdh23erl/erl小鼠，进一步检测pHBSP对听力的保护作用，评估用药效果，确定最佳用药方式和药物安全性，阐明pHBSP听力保护的分子作用机制，为开发有效的听力保护药物提供必要的工作基础。

中文关键词： 动物模型；治疗；听力；毛细胞；细胞凋亡

英文摘要： Hearing loss is one of the most common sensory disorders and there are currently no efficient drugs for the treatment. The Cdh23erl/erl mice are a novel mouse model for hearing loss with the mutation of the cadherin 23 (Cdh23) gene and are characterized by progressive hearing loss beginning from postnatal day 27. The short interval from initial hearing loss to deafness (p27–p90) makes this model ideal for screening and validating otoprotective drugs. Our previous study showed that erythropoietin (EPO), which is used to treat Cdh23erl/erl mice in our lab, could ameliorate inner ear hair cell loss and improve hearing (Neuroscience. 2013 May 1; 237:1-6). However, the erythropoietin has side effect of thrombotic complications. pHBSP, a EPO derivative, is tissue protective without the hematopoietic side effect. Moreover, its application in hearing protection has not been reported. This project will further test the otoprotective effect of pHBSP in Cdh23erl/erl mice, seeking the best route of administration, evaluating drug safety, and elucidating the molecular mechanism of pHBSP for hearing protection. Finally, this project will provide necessary foundation for the development of otoprotective drugs.

英文关键词： animal model;therapy;hearing ;hair cells;apotosis