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

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200μmol/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。

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 200μmol/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.