顺铂肾损伤（CisAKI）发病机制复杂，临床缺乏有效干预药物，研究的主要瓶颈之一是CisAKI干预药物常同时干扰了顺铂的抗肿瘤作用；而以人近端肾小管上皮细胞特异性铂转运蛋白为靶点研究CisAKI的发病与干预可以规避顺铂的抗肿瘤作用。文献和我们前期研究均证实人源性肾脏类器官模型是体外研究铂转运蛋白的良好工具，因此我们推测以人肾脏类器官为模型可以从铂转运蛋白角度研究CisAKI的特异性发病机制，并可能筛选到有临床应用前景的干预药物。本项目将以患者肾脏类器官为研究对象，采用定量蛋白质组学技术，比较发生CisAKI和未发生CisAKI的肺癌患者肾脏类器官膜蛋白表达差异，从中筛选并验证特异性铂转运蛋白参与CisAKI发病的机制；并以转运蛋白为靶点，对既往文献报道过的能抑制转运蛋白功能的系列商品化药物进行筛选，初步获得CisAKI候选干预药物。本项目将为CisAKI的发病和防治研究提供新的思路和策略。

Although extensive researches on cisplatin-induced acute kidney injury (CisAKI) have been studied previously, its pathogenesis is still complex, and effective intervention drugs are rare in clinics. One of the main challenges of these studies is that the intervention drugs of CisAKI often compromise the anti-tumor effect of cisplatin. Considering the crucial role cisplatin transporters play in the entry of cisplatin into tubular cells, it is believed that targeting these transporters for a renoprotective strategy may not affect the anti-tumor effects of cisplatin. Literature and our previous studies have confirmed that the human kidney organoid model is a good in vitro model for studying cisplatin transporters. Using patients’ kidney organoid model, our present project will focus on CisAKI and cisplatin transporters. We will use quantitative proteomics technology to compare the difference of transporter expression of kidney organoid between CisAKI and non-CisAKI lung cancer patients, and screen and verify the mechanism of the specific transporter involved in the pathogenesis of CisAKI. We will further test and screen whether commercialized drugs that selectively inhibit transporters could effectively reduce the entry of cisplatin into the renal tubular cells and protect from CisAKI. This study is not only expected to find the specific pathogenesis of CisAKI, which is different from cisplatin's anti-tumor effect, but also to obtain potential interventional drugs with clinical application prospects.