Sirt3诱导线粒体自噬拮抗顺铂致听觉上皮细胞损伤的作用及机制研究

顺铂耳中毒性聋作为一种不可逆性的听力损伤，严重影响众多接受顺铂化疗的肿瘤患者的生存质量，目前临床上尚无有效的防治手段。我们在国际上率先发现诱导自噬可减轻顺铂致听觉上皮细胞损伤，并在本项目的预实验中发现上调sirt3可能通过诱导线粒体自噬拮抗顺铂耳毒性，但具体机制不明。我们拟在此基础上：1.探明线粒体自噬在上调sirt3拮抗顺铂致听觉上皮细胞损伤中的作用；2.阐明听觉上皮细胞中sirt3对线粒体自噬的调节机制；3.在动物模型中揭示靶向干预听觉上皮细胞中sirt3-线粒体自噬信号对顺铂耳中毒性聋的预防作用。本项目的研究成果将阐明sirt3-线粒体自噬信号在顺铂致听觉上皮细胞损伤中的作用及机制，为顺铂耳中毒性聋防治策略的探索提供重要的实验基础。

Cisplatin-induced ototoxicity, as a kind of irreversible hearing impairment, seriously affects the quality of life of many tumor patients receiving cisplatin chemotherapy, and there is no effective treatment in clinical practice. We are the first in the world to discover that enhancing autophagy can alleviate cisplatin-induced ototoxicity, and found in previous studies that up-regulation of sirt3 may mitigate cisplatin-induced ototoxicity by inducing mitophagy, but its mechanism is unknown. We intend to further explore the role of mitophagy in alleviating effects of upregulating sirt3 on cisplatin-induced ototoxicity, the regulatory mechanism of sirt3 on mitophagy in auditory epithelial cells, and the prevention effect of upregulating sirt3-mitophagy signal on cisplatin-induced ototoxicity in rats. The results of this research will clarify the role and mechanism of sirt3-mitophagy signal in cisplatin-induced ototoxicity, and provide an important experimental basis for the development of prevention strategies on cisplatin-induced ototoxicity.