Aspirin与自噬通路及核转录因子FoxG1在听觉系统退行性变中的协同调控机制研究

Degeneration of the auditory system is the most common cause of acquired deafness. At present, clinical studies have found that Aspirin can improve the health status and play an important role in the prevention and treatment of various diseases. In the auditory system, small doses of Aspirin have protective effects on the nervous and auditory system, and high doses of Aspirin have obvious side effects of the auditory system, but this different dose caused different clinical manifestations of the underlying mechanisms have not been fully elucidated. In addition, mitochondrial DNA loss and nuclear transcription factor abnormalities caused by mitochondrial dysfunction are closely related with senile deafness, studies have shown that autophagy is an important way of cell self-protection. However, the absence of mitochondrial DNA mutations in the inner ear, the existence of synergistic regulation between Aspirin, autophagy pathway and nuclear transcription factors and the molecular mechanism of Aspirin in the auditory system protection are rarely reported. This project takes D-galactose-induced mouse and cell aging model as research object, and explores the synergistic regulation of Aspirin and autophagy pathway and nuclear factor in hair cell degeneration.

听觉系统退行性变是导致后天性耳聋最常见的原因。目前临床研究发现Aspirin能够改善健康状况，在多种疾病防治中起着重要作用。在听觉系统中，小剂量Aspirin对神经和听觉系统有保护作用,高剂量的Aspirin则具有较明显的听觉系统毒副作用，但这种因不同剂量引起不同临床表现的内在机制尚未完全阐明。另外，线粒体DNA的缺失及核转录因子的异常引起的线粒体功能障碍都与老年性聋有着密切关系，有研究表明自噬是细胞自我保护的重要途径。但是，在内耳中线粒体DNA突变缺失、Aspirin、自噬通路、核转录因子之间是否存在协同调控关系及Aspirin在听觉系统的保护中的分子机制却鲜有报道。本项目以D-半乳糖诱导小鼠及细胞衰老模型为研究对象，探讨了Aspirin与自噬通路及核转录因子在毛细胞衰老过程中的协同调控作用。

听觉系统退行性变是导致后天性耳聋最常见的原因。目前临床研究发现Aspirin能够改善健康状况，在多种疾病防治中起着重要作用，但在老年性聋中的作用机制仍待阐明。另外，在内耳中线粒体DNA突变缺失、Aspirin、自噬通路、核转录因子之间是否存在协同调控关系及Aspirin在听觉系统的保护中的分子机制却鲜有报道。本项目以D-半乳糖诱导小鼠及细胞衰老模型为研究对象，探讨了Aspirin与自噬通路及核转录因子FoxG1在毛细胞衰老过程中的协同调控作用。我们发现在听觉系统退行性变过程中，Aspirin可通过激活毛细胞中FoxG1和自噬信号的保护机制，促进其在老化进程中的存活能力。我们还发现FoxG1通过激活自噬通路抑制了老化毛细胞对炎症刺激的易感性，从而发挥维持细胞存活的作用。本研究有助于老年性聋相关分子机制的阐明，同时也为老年性聋的临床防治提供了新的靶点。

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