关键词: 精胺/亚精胺N1-乙酰转移酶1, 顺铂, 氧化应激, 细胞凋亡

Abstract: Objective To investigate the role and mechanism of spermidine/spermine N1-acetyltransferase 1 （Sat1） in cisplatin （DDP）-induced injury of mouse cochlea-derived immortalized auditory epithelial cells （HEI-OC1）. Methods HEI-OC1 cells were divided into four groups： siNC, siSat1, siNC+DDP, and siSat1+DDP. Cell proliferation was measured by CCK-8 assay; intracellular reactive oxygen species （ROS） levels were detected using DCFH-DA fluorescent probe; mRNA expression levels of Sat1, catalase （CAT）, and glutathione peroxidase 1 （GPx1） were assessed by qPCR; protein expression of Sat1 and apoptosis-related proteins, including B-cell lymphoma-2 （Bcl-2）, Bcl2-associated X protein （Bax）, cysteinyl aspartate-specific proteinase-3 （Caspase-3）, and cleaved Caspase-3, were detected by Western blotting, and the ratios of cleaved Caspase-3/Caspase-3 and Bcl-2/Bax were calculated. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity were measured by ELISA to evaluate oxidative stress. Results Compared with the siNC group, the siSat1 group showed downregulated Sat1 mRNA and protein expression, decreased basal ROS and MDA levels, increased SOD activity and CAT and GPx1 mRNA expression, and reduced Bax and Cleaved Caspase-3 protein expression （all P < 0.05）. After DDP treatment, the siNC+DDP group exhibited decreased cell viability, elevated ROS and MDA levels, reduced SOD activity and CAT and GPx1 mRNA expression, and increased Bax and cleaved Caspase-3 protein expression; all these alterations were significantly reversed in the siSat1+DDP group （all P < 0.05）. Conclusion Sat1 plays a critical role in DDP-induced HEI-OC1 cell apoptosis by mediating oxidative stress.

Key words: spermidine/spermine N1-acetyltransferase 1, cisplatin, oxidative stress, apoptosis