一线抗肿瘤药物顺铂可导致严重的急性肾损伤，其发生率高且治疗手段缺乏，极大限制了其临床应用。因此，研究顺铂引起急性肾损伤的发病机制推动该类毒性的克服有着重大的临床需求。我们前期发现OPTN蛋白在顺铂引起的急性肾损伤小鼠肾脏和肾小管上皮细胞HK-2中表达显著增加，而Optn基因敲除小鼠中顺铂引起的急性肾损伤明显加重，该作用可能与OPTN蛋白功能缺失进而抑制NDP52最终导致自噬过程受损有关。基于此，本课题将进一步明确OPTN在顺铂引起的急性肾损伤中扮演的角色，阐明OPTN调控NDP52促进自噬减轻顺铂引起急性肾损伤的分子机制，并证实OPTN作为顺铂引起急性肾损伤治疗靶点的可能性。通过本课题的研究，不仅将明确OPTN蛋白在顺铂急性肾损伤发生发展中的作用，还将揭示OPTN激活NDP52促进自噬的全新生物学功能，并为将OPTN作为药物靶点，设计与发现顺铂引起的急性肾损伤新型治疗药物提供理论依据。

Cisplatin, a first-line anti-tumor drug, can cause severe acute kidney injury, and its clinical application is limited owing to the high incidence and lack of treatment of this side effect. Therefore, studying the mechanism of acute kidney injury caused by cisplatin can promote to overcome this kind of toxicity. We previously found that OPTN expression was significantly increased in the kidney of mice injured by cisplatin and cisplatin-treated HK-2 cells. Moreover, acute kidney injury of cisplatin was significantly aggravated in Optn knockout mice, this process might be related to OPTN deficiency which leads to inhibition of NDP52 and further affects autophagy. this research will not only reveal the role of OPTN in the development of cisplatin-induced acute kidney injury, but also illuminate a new biological function of OPTN activating NDP52 to further promote autophagy. Furthermore, it also provides a theoretical basis for designing and discovering new cisplatin-induced acute kidney injury drugs targeting OPTN.