遗传和环境因素共同作用是噪声性听力损失易感的重要因素。GJB2基因p.V37I突变是导致听力下降的重要遗传易感性突变。前期，我们发现GJB2 p.V37I 基因敲入小鼠对噪声性听力下降更易感，尤其是GJB2p.V37I KI小鼠耳蜗的NNMT基因特异性高表达。结合Sirt1是NNMT代谢产物MNAM的靶蛋白，以及Sirt1/Foxo3a通路与氧化应激密切相关的报道。我们推测：耳蜗中Sirt1基础含量增高是GJB2p.V37I KI小鼠噪声易感性的分子基础，而Sirt1/Foxo3a通路调节的耳蜗细胞氧化应激反应是其噪声易感性的可能机制。本课题拟通过我们特定噪声暴露模式建模，观察GJB2p.V37I KI小鼠的听力表型和Sirt1/Foxo3a通路介导的耳蜗细胞氧化应激损伤反应的对应关系，探究Sirt1/Foxo3a通路在其噪声易感性中的作用机制，为噪声性听力损失防治提供新思路。

The susceptibility to noise induced hearing loss differs among individuals and appears to be due to the combination of genetic and environmental factors. p.V37I variant of GJB2 gene is one of the most important genetic susceptibility mutant. We previously established GJB2 p.V37I knock in(KI) mice model and found they are susceptibility to noise induced hearing loss, further more certified its specific over-expression of NNMT gene in the cochlear. Sirt1 may be the target protein of MNAM, the product of NNMT. Sirt1/Foxo3a is related to antioxidant and redox signaling. Thus, we hypothesized that Sirt1 is highly molecular to account for the susceptibility of noise induced hearing loss in GJB2 p.V37I KI mice. The response of Sirt1/Foxo3a to the oxidative stress may be the possible mechanism of the susceptibility of noise-induced hearing loss with GJB2p.V37I.This study will establish the noise induced hearing loss model with our special noise exposure pattern, record the relationship between the hearing and the response of Sirt1/Foxo3a to oxidative stress, in order to explore the role and mechanism of Sirt1/Foxo3a in the susceptibility of noise induced hearing loss in GJB2 p.V37I KI mice and provide new ideas for the prevention and treatment of noise hearing loss.