丹参素钠对顺铂耳毒性抑制作用的实验研究
Experimental Study on the Inhibitory Effect of Sodium Danshensu on Ototoxicity of Cisplatin
郭娜 1胡俊 2刘子熠 3付小龙 3夏明1
作者信息
- 1. 耳鼻咽喉头颈外科 山东第一医科大学附属省立医院,济南 250021
- 2. 温州医科大学,温州 325035
- 3. 山东第一医科大学,济南 250102
- 折叠
摘要
目的 探讨丹参素钠(SDSS)对顺铂耳毒性的抑制作用.方法 选取 HEI-OC1 细胞系构建顺铂诱导的损伤模型,确定顺铂在 24h对 HEI-OC1 细胞的 50%最大抑制浓度(IC50),基于该模型在小分子化合物库中筛选具有保护作用的药物.在 HEI-OC1 细胞模型和小鼠耳蜗外植体毛细胞顺铂损伤模型中,检测 SDSS对毛细胞存活率和凋亡水平的影响.采用超氧化物阴离子荧光探针(DHE)染色检测 SDSS 对顺铂诱导的 HEI-OC1 细胞氧化应激水平的影响并选用药物 N-乙酰半胱氨酸(NAC)作为阳性对照.结果 从 210 种 FDA批准的小分子化合物中筛选出具有显著保护作用的药物 SDSS,SDSS预处理可有效抑制顺铂诱导的 HEI-OC1 细胞凋亡、活性降低以及细胞内活性氧(ROS)升高,其最佳浓度为 200 μmol/L.此外,SDSS 可抑制顺铂对耳蜗基底膜外植体毛细胞的损伤.结论 SDSS可能通过抑制毛细胞内 ROS升高并抑制细胞凋亡,从而发挥对顺铂所致耳毒性的抑制作用.
Abstract
Objective To investigate the inhibitory effect of Sodium Danshensu(SDSS)on ototoxicity of cisplatin.Method HEI-OC1 cell lines were selected to construct cisplatin-induced damage models based on which protective agents were screened in the small-molecule compound library and Determination of IC50 of cisplatin in HEI-OC1 cells at 24 h.The effect of SDSS on hair cell survival was measured in HEI-OC1 cell models and cisplatin-induced mouse cochlear implant models.The effect of SDSS on cisplatin-induced oxidative stress levels in HEI-OC1 cells was measured by superoxide anion fluorescence probe(DHE)staining and the positive control was NAC.Result SDSS,a potent protective agent,was selected from 210 FDA-approved small molecule compounds,and SDSS pretreatment significantly inhibited cisplatin-induced decrease in HEI-OC1 cell activity,apoptosis and reactive oxygen species(ROS)aggregation at an optimal concentration of 200 μmol/L.In addition,SDSS significantly inhibits cisplatin-induced damage to hair cells in mouse cochlear explants.Conclusion SDSS may play a protective role in cisplatin-induced ototoxicity by inhibiting ROS aggregation and apoptosis in hair cells.
关键词
顺铂/耳毒性/丹参素钠/活性氧Key words
cisplatin/ototoxicity/SDSS/reactive oxygen species引用本文复制引用
出版年
2024
NETL
NSTL
维普
万方数据