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 HEIOC1 cell models and cisplatin-induced mouse cochlear implant models. The effect of SDSS on cisplatininduced 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.

Key words: cisplatin, ototoxicity, SDSS, reactive oxygen species 

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 24 h 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。

关键词: 顺铂, 耳毒性, 丹参素钠, 活性氧