甲泼尼龙琥珀酸钠通过Notch2/hes1信号通路减轻庆大霉素致耳蜗毛细胞损伤

Methylprednisolone alleviates cochlear hair cell damage caused by gentamicin through Notch2/hes1 signaling pathway

目的探究甲泼尼龙琥珀酸钠(MP)对庆大霉素(GM)致耳蜗毛细胞损伤的影响和机制。方法将耳蜗毛细胞随机分为对照组(正常培养状态耳蜗毛细胞)、模型组(3 mmol·L^(-1)庆大霉素)和实验组(3 mmol·L^(-1)庆大霉素和0.2 mg·L^(-1)甲泼尼龙琥珀酸钠)。以CCK-8法检测细胞增殖抑制率,Western blot检测半胱氨酸蛋白酶-3(Caspase-3)、Notch2和hes1蛋白的表达。结果模型组和实验组的细胞增殖抑制率在72 h时分别为(33.43±2.17)%和(17.43±4.23)%;对照组、模型组和实验组Caspase-3的相对表达量分别为1.01±0.02,1.79±0.18和1.21±0.14;Notch2的相对表达量分别为1.03±0.05,1.69±0.11和1.15±0.09;hes1相对表达量分别为1.02±0.06,1.58±0.12和1.11±0.07。模型组与对照组相比,实验组与模型组相比,差异均有统计学意义(均P<0.05)。结论甲泼尼龙琥珀可通过下调耳蜗毛细胞Notch2和hes1的表达,促进细胞增殖并抑制细胞凋亡,保护庆大霉素引起的耳蜗毛细胞损伤。

Objective To explore the effects of methylprednisolone(MP)on cochlear hair cell damage caused by gentamicin(GM)and the mechanism.Methods The cochlear hair cells were randomly assigned to control group(normally cultured cochlear hair cells),model group(3 mmol·L^(-1) GM)and test group(3 mmol·L^(-1) GM and 0.2 mg·L^(-1) MP).CCK-8 method was used to detect the inhibition rate of cell proliferation.Western blot was used to detect the expression of Caspase-3,Notch2 and hes1 protein.Results In the model group and the test group,the cell proliferation inhibition rates were(33.43±2.17)%and(17.43±4.23)%at 72 h,respectively;in the control group,model group and test group the relative expression of Caspase-3 were 1.01±0.02,1.79±0.18 and 1.21±0.14,respectively;the relative expression of Notch2 were 1.03±0.05,1.69±0.11 and 1.15±0.09;the relative expression of hes1 were 1.02±0.06,1.58±0.12 and 1.11±0.07,respectively.The differences between the model group and the control group,as well as between the test group and the model group were statistically significant(P<0.05).Conclusion MP can reduce the expression of Notch2 and hes1 in cochlear hair cells to promote cell proliferation and inhibit cell apoptosis,thus protecting cochlear hair cells from damage caused by GM.