老年性耳聋（Age-related hearing loss，ARHL）的机制不明。研究表明，衰老诱导耳蜗miR-34a表达增强，耳蜗细胞凋亡，最终听力下降。我们发现小鼠耳蜗中蛋白磷酸酶1核目标亚基（PNUTS）是miR-34a的直接靶点，且PNUTS的表达呈年龄依赖性下降，同时端粒重复序列结合因子2(TRF2)表达也显著减少，与耳蜗细胞凋亡率呈正相关。据此，我们推测miR-34a / PNUTS / TRF2通路可能参与了ARHL的发生发展。临床研究和我们前期实验均提示，山茱萸提取物可有效防护ARHL，但其机制有待阐明。综上，本课题拟利用转基因小鼠，初步探讨miR-34a / PNUTS / TRF2通路在ARHL中的作用及山茱萸提取物对ARHL的防护机制，为临床防治ARHL和推广中药的开发应用，提供新的实验依据。

Age-related hearing loss (ARHL) is associated with age-related hearing loss, the mechanism is unknown. We found that senescence could enhance miR-34a expression and induced cochlea apoptosis. Protein phosphatase 1 nuclear targeting subunit (PNUTS) is a key regulator of protein phosphatase 1, as a direct downstream target of miR-34a and is involved in the regulation of cell apoptosis. The expression of PNUTS in the cochlea was decreased during the senescence, and the expression of telomere repeat binding factor 2 (TRF2) was also inhibited, and it was positively correlated with the apoptotic rate. Accordingly, we conclude that the miR-34a / PNUTS / TRF2 pathway may be involved in the ARHL process. Clinical studies and our early results suggest that Corni Fructus extract as a traditional Chinese medicine preparation, can effectively protect ARHL, but its protective mechanism remains to be elucidated. This project intends to investigate the role of miR-34a/PNUTS/TRF2 pathway in ARHL and the protective mechanism of Corni Fructus extract by using transgenic mice, so as to provide new route for clinical prevention and treatment of ARHL.