基于“肾开窍于耳”的理论基础，本项目拟开展雌激素对听力调节的分子信号通路研究。前期结果发现，大鼠去卵巢后外毛细胞内雌激素受体和动力蛋白Prestin表达水平降低。文献提示环磷腺苷效应元件结合蛋白（CREB）的磷酸化是雌激素信号通路的终末转录分子，且该蛋白是雌激素相关PI3k和SIRT1下游的主要转录分子。因此本项目拟论证雌激素可通过CREB的磷酸化调控耳蜗外毛细胞内Prestin表达，进而导致该细胞神经兴奋性变化，最终影响听力。本项目借助电生理方法检测大鼠听阈和耳蜗外毛细胞功能；在体水平特异性抑制和过表达外毛细胞内CREB以验证雌激素需通过该蛋白磷酸化的激活调控Prestin；细胞水平以Calcium sensor荧光探针研究雌激素对耳蜗外毛细胞声能转化为神经电信号作用的机制。本项目阐述了雌激素对听力影响的分子机制，为耳-肾的藏窍学说提供现代科学依据，具有重要的科学、社会和间接经济意义。

Based on the theory of "Kidney opening at ear", this topic explores the molecular pathways of estrogen on hearing regulation. According to the results of previous work, the expression levels of estrogen receptor and Prestin in outer hair cells of cochlea after ovariectomy were reduced in rats. The literature suggests that phosphorylation of the cyclophosphine adenosine response element binding protein (CREB) is the final terminal transcription molecule of estrogen in the intracellular signaling pathway, and that this protein is the most important transcription molecule downstream of the estrogen-related PI3k and SIRT1 pathway. Therefore, this project intends to demonstrate that estrogen can regulate the expression of Prestin in outer hair cells of the cochlea through phosphorylation of CREB, and then affect the neuronal excitability of the cell, and eventually affect hearing. This project uses electrophysiological methods to detect rat hearing and cochlear outer hair cell function. Specific inhibition and over-expression of CREB in cochlear hair cells at the body level to verify that estrogen needs to regulate and regulate Prestin through phosphorylation of this protein; the cell level is calculated using a calcium sensor Fluorescent probe method was used to explore the role of estrogen in regulating the conversion of acoustic energy from outer cochlear hair cells into neural electrical signals. This project lays the foundation for elaborating the molecular mechanism of the effect of estrogen on hearing, provide modern scientific basis for the ear-kidney theory, which has important scientific, social and indirect economic significance.