去乙酰化酶Sirtuin 1对老年性聋的治疗作用及其机理的研究

老年性聋是影响人类生活质量的主要疾病之一，其发病机制不明，尚无有效的防治措施。研究表明线粒体DNA常见缺失（CD）在听觉系统的累积是导致老年性聋的重要原因。我们最近的研究发现D-半乳糖诱导的老化大鼠内耳CD增加的同时，去乙酰化酶Sirtuin 1表达显著降低，而过表达Sirtuin 1的内耳螺旋神经节细胞则可有效对抗CD累积。这些研究结果提示Sirtuin 1具有通过减少CD在听觉系统累积进而达到防治老年性聋的作用。在本课题中，我们计划进一步探讨去乙酰化酶Sirtuin 1对老年性聋的治疗作用及其作用机理。主要内容包括：①建立听觉系统CD细胞系和动物模型，检测Sirtuin 1基因转染对CD累积的抑制作用和对听功能的保护作用；②探讨Sirtuin 1减少CD累积的机理；③探讨Sirtuin 1对老年性聋的治疗作用机理。本项目将为老年性聋发病机制的研究提供新的思路，为临床治疗提供新的靶点。

Presbycusis is one of the most common diseases affecting the living quality of general people. At present, the pathogenesis of presbycusis is unclear, and there are no effective methods to prevent or treat it. Recent researches indicate that the increase of mitochondrial DNA common deletion (CD) in the auditory system is an important causal factor for presbycusis. In the preliminary studies, we found that the expression of Deacetylase Sirtuin 1 was significantly decreased with the accumulation of CD in the inner ear of D-galactose-induced aging rats, and the spiral ganglion cells of Deacetylase Sirtuin 1 over-expression could effectively prevent the accumulation of CD. These findings implicate that Deacetylase Sirtuin 1 may have the ability to prevent or treat presbycusis by reducing the accumulating of CD in the auditory system. In this study, we plan to further investigate the therapeutical effects of Deacetylase Sirtuin 1 on presbycusis and its underlying mechanism in the designed project. The study aims includes: ① CD cellular models and animal models of auditory system will be developed; the inhibition of CD and the protection of auditory capacity induced by Sirtuin 1 gene transfection will be evaluated. ② To investigate into the mechanism of Sirtuin 1 in reducing the accumulation of CD. ③ To investigate into the mechanism of Sirtuin 1 in treating presbycusis. This study provides new insights into the pathogenesis of presbycusis, and also provides new target of clinical treatment for presbycusis.