中华耳科学杂志2025，Vol.23Issue(9)：1045-1052,8.DOI:10.3969/j.issn.1672-2922.2025.09.008
基于NLRP3/Caspase-1/GSDMD通路探讨顺铂耳毒性的焦亡机制
Mechanisms of pyroptosis in cisplatin ototoxicity based on the NLRP3/Caspase-1/GSDMD pathway
摘要
Abstract
Objective To investigate damaging toxic effects of cisplatin on House Ear Institute-Organ of Corti 1(HEI-OC1)cells and potential mechanisms.Methods In this study,a model of HEI-OC1 cell injury by cisplatin was established.The Caspase-1 inhibitor VX-765 was used as intervention.The CCK-8 method was used to identify cell viability.Flow cytometry,LDH release assay,and AO/EB fluorescence staining were used to examine cellular membrane integrity.ELISA,Western-Blot,immunofluorescence and qRT-PCR were used to demonstrate expression of pyroptosis-related proteins and its mRNAs.Results Compared with the control,cisplatin treated cells demosntrated decreased survival,with some cells showing increased membrane permeability,swelling and deformation or cell membrane rupture.Expression of pyroptosis-related proteins and mRNAs was increased(P<0.05).Compared with cisplatin treatment only,cells treated with VX-765+cisplatin showed increased survival with decreased expression of pyroptosis-related proteins and mRNAs(P<0.05).Conclusions Cisplatin induced death of HEI-OC1 cells in a concentration-dependent manner.Caspase-1-mediated cellular pyroptosis plays an important role in cisplatin-induced ototoxicity,potentially by regulating the NLRP3/Caspase-1/GSDMD pathway.关键词
毛细胞/顺铂/耳毒性/焦亡/听力损失Key words
hair cell/cisplatin/ototoxicity/pyroptosis/hearing loss引用本文复制引用
符昌学,张亚男,田美慧,刘欢,孙维芳,李锟,彭后能,汤勇..基于NLRP3/Caspase-1/GSDMD通路探讨顺铂耳毒性的焦亡机制[J].中华耳科学杂志,2025,23(9):1045-1052,8.基金项目
吉林省卫生健康委员会项目(2022JC034) （2022JC034）
国家级大学生创新创业训练计划项目(202310199040) （202310199040）
