内耳椭圆囊毛细胞损伤在前庭功能疾病中起关键作用。椭圆囊毛细胞在损伤后具有有限的再生能力，然而对如何调控损伤后毛细胞功能性再生以及促进前庭功能的修复却仍不清楚。我们前期研究表明，毛细胞Espin1基因 和Notch信号通路，在椭圆囊毛细胞损伤后促进毛细胞以及纤毛再生中起关键作用。在此基础上提出假设，协同调控Espin1和Notch信号可促进椭圆囊功能性毛细胞再生以及前庭功能修复。本项目拟通过腺病毒转染上调毛细胞Espin1基因并结合Notch信号通路的抑制剂下调Notch信号水平，采用转基因小鼠，谱系追踪，免疫荧光染色，q-PCR，扫描电镜，VsEP等方法进行研究，来探索其在新生和成年小鼠离体及活体椭圆囊损伤模型中，对功能性毛细胞以及纤毛再生的协同调控机制；并进一步阐明毛细胞损伤后前庭功能修复的机制，为临床上通过基因和药物治疗前庭功能疾病提供新的思路和理论依据。

Hair cells are mechanosensitive cells required for balance functions. Dysfunction or loss of hair cells is the primary cause of balance dysfunction. Limited regeneration takes place in the mammalian utricle, yet the underlying pathology of how to induce functional hair cell regeneration, furthermore recover the vestibular function after hair cell loss is still not clear. Preliminary data shows that Espin1 gene and Notch signal pathway can regulate hair cell and bundle regeneration after hair cell loss. Based on previous studies, this proposal will investigate the functional hair cell regeneration by regulation of Espin1 gene and Notch signaling pathway with the goal of vestibular function recovery. In our research proposal, Adenovirus transfection will be used to overexpression Espin1 gene and Notch inhibitor will be used to down-regulate the Notch signal pathway expression, combine with transgenic mouse, lineage tracing experiment, immunoflurensence staining, q-PCR, SEM and VsEP to determine whether it can enhance functional hair cell and bundle regeneration in the damaged neonatal, adult mouse utricle both in vitro and in vivo, furthermore to elucidate the mechanisms of vestibular function recovery, which provides a new idea of repairing balance dysfunction with gene and drug treatment.