顺铂作为广泛应用的抗肿瘤药，可通过促进肾小管上皮细胞的坏死及炎症反应，导致急性肾损伤（AKI）的发生。然而目前顺铂导致肾毒性仍缺乏有效的防治手段。焦亡作为一类炎症性的细胞坏死方式，在诱导细胞坏死同时可释放炎症因子，进一步加重损伤。有研究发现包括顺铂在内的多种化疗药可引起正常组织细胞的焦亡，从而产生毒副作用。而GSDME可能是其主要的效应分子，并且我们在前期的预实验发现，随着顺铂损伤浓度的加重，GSDME的活性端表达显著上调，同时炎症性caspase-11活性也随着增加，那么我们推测caspase-11可能通过调控GSDME介导顺铂诱导的肾小管上皮细胞焦亡。本项目将为今后临床防治化疗药所导致的肾毒性奠定理论基础。

Tubular cell necrosis and inflammation are the major pathophysiology of cisplatin-induced acute kidney injury (AKI). But there has been lack of effective preventive and therapeutic method of AKI. Pyroptosis is a form of necrotic and inflammatory programmed cell death. The normal cells can suffer from pyroptosis induced by chemotherapy drugs through cleavage of GSDME. In the preliminary experiment, we found the active form of GSDME increased with growing dose of cisplatin，as well as cleaved-caspase-11. In order to provide the new idea and strategy for treatment of cisplatin-induced AKI, we would test the speculation that tubular pyroptosis could be executed by caspase-GSDME.