衰老蛋白p66shc在D-半乳糖诱导大鼠内耳及血管纹边缘细胞老化中的作用及其机制的研究

Age-related hearing loss (ARHL) or presbycusis is the most common sensory deficit in the elderly, and it has become a severe.social and health problem. We have previously utilized overdoses of D-galactose (D-gal) to induce an aging model of rats, which harbor increased amounts of the mtDNA 4834-bp deletion in the central and peripheral auditory system.The p66Shc protein is a Src homologue and collagen homologue (Shc) adaptor protein, which has the ability to interact with other proteins that mediate cell signaling, and P66shc-null mice display an increased lifespan and enhanced resistance to oxidative stress. We have found that p66shc was expressed in the Stria Vascularis of the cochlear of mice, and it may participate in the formation of presbycusis. In these study, at the foundation of previous study, we use the D-galactose-induced inner ear aging and the marginal cell senescence model to find the role and the mechenism of p66shc in presbycusis.

随着社会的进步，老年性聋越来越成为一种严重影响人们生活质量的疾病。如何提高老年人的生活及生命质量成为我国卫生事业关注的重要问题。深入的研究老年性聋的发生机发展机制，从而找寻治疗老年性聋的方法，对提高老年人的生活和生命质量有着重要的意义。D-半乳糖内耳拟老化模型是目前使用广泛的一种人工拟老化模型，具有衰老体征明显，模型诱导稳定，耗时短的特点。衰老蛋白p66shc是第一个被证实敲除后可以延长小鼠寿命且保护其免患多种衰老相关疾病且无明显副作用的与衰老相关的蛋白。本课题前期的我们对衰老蛋白p66shc在小鼠耳蜗中的表达发现，其在外侧壁血管纹细胞中有表达。而利用D-半乳糖诱导的老化小鼠模型的研究发现，p66shc可能参与了内耳老化的过程。本项目拟在前期研究的基础上，利用D-半乳糖诱导的耳蜗血管纹边缘细胞及大鼠内耳老化模型，以及基因抑制技术研究p66shc参与老年性聋的作用及可能机制及其作用。