噪声、药物、感染等均能造成明显耳毒性和永久性听力障碍，因此深入了解毛细胞损伤机制及有效毛细胞保护策略在感音神经性聋的防治工作中尤为重要。前期研究发现下调组蛋白H3K9me2能有效减轻耳蜗毛细胞损伤，达到毛细胞保护的目的；基因表达谱分析发现细胞周期调控基因Pcdh8和Insm1在毛细胞保护中表达显著上调。最新研究表明，细胞周期调控基因是维持分裂后毛细胞稳定的重要因素。本研究旨在研究调控组蛋白H3K9me2毛细胞保护的分子机制及有效的毛细胞保护策略：通过观察shRNA和G9a/GLP抑制剂处理后毛细胞的形态和数量，研究Pcdh8、Insm1基因与组蛋白H3K9me2的相互作用，阐明其对毛细胞损伤和保护的调控作用，并进一步探讨其作用的分子机制；同时，在耳蜗过量表达Pcdh8和Insm1基因，实现G1/S期阻滞，促进毛细胞自我修复，逆转毛细胞死亡，为基因治疗感音神经性耳聋奠定实验基础。

Sensorineural hearing loss (SNHL) is one of the most common sensory defects in humans. Hair cells are vulnerable to various ototoxic insults, such as noise, drugs and infections. Relative mechanism and effective prevention of hair cell loss remains an unmet medical need. Previous studies have found that cell cycle-related genes are quite important to maintain the stability of hair cells. It was found that down-regulation of the dimethylated histone H3 lysine 9 (H3K9me2) can effectively reduce the cochlear hair cell injury and protect hair cells. Expression profiling and RT-qPCR analyses indicated that the otoprotection by G9a/GLP inhibition might be mediated through the up-regulation of Pcdh8 and Insm1. It was confirmed that the expression Pcdh8 and Insm1 can induce G1/S phase arrest in our previous studies. Using shRNA interference and the G9a/GLP specific inhibitors, we try to observe the changes of cell cycle-related genes expression and histone modification, as well as the interaction, to further understand the molecular mechanisms underlying the otoprotection of inhibition of H3K9me2. Moreover，the project is to explore the potential therapeutic value of Pcdh8 and Insm1 clinically for hearing protection of Corti organ morphologically and functionally by over expression of Pcdh8 and Insm1.