α-硫辛酸对卡那霉素致毒小鼠耳蜗磷酸化p38MAPK表达的影响

摘要

Objective To investigate the effect of a-lipoic acid (LA) on kanamycin (KM) -induced expression of phosphorylated p38 mitogen-activated protein kinase (p38MAPK) in mouse cochlea, and explore the protective role and molecular mechanism of LA on KM-induced ototoxicity. Methods 20 BALB/C mice were randomly divided into control, KM, KM plus LA and LA groups. Mice from each group were continuously given drugs by subcutaneous injection twice daily for 14 days. Expression of phosphorylated p38MAPK in mouse cochlea was detected by the SABC method of immunohistochemistry and microscope image analysis technique. Auditory threshold was tested by auditory brainstem response (ABR) measurement. Results Expression of phosphorylated p38MAPK and ABR threshold shift in KM plus LA group were both significantly declined as compared with those of KM group (P <0. 01). Moreover, change of pp38MAPK expression was in high correlation with that of ABR threshold shift ( I r I > 0. 7, P < 0. 05, P < 0. 01). Conclusions LA could effectively attenuate KM ototoxicity by inhibiting phosphorylated p38MAPK high-expression induced by KM, this might be one of the molecular mechanisms by which LA could protect against KM ototoxicity%目的 研究α-硫辛酸(LA)对卡那霉素(KM)致毒小鼠耳蜗磷酸化p38MAPK表达的影响,探讨LA对KM耳毒性损伤的防护作用及其分子机制.方法 20只BALB/c小鼠随机分成对照组、KM组、KM +LA组和LA组,各组动物均连续皮下注射给药14 d,每天2次；应用免疫组织化学SABC法及显微图像分析技术观察耳蜗中磷酸化p38MAPK的表达,同时结合听脑干反应(ABR)测试观察用药前后小鼠听阈的变化.结果 KM+LA组小鼠耳蜗磷酸化p38MAPK表达和ABR阈移均明显低于KM组(P＜0.01)；且磷酸化p38MAPK表达变化与ABR阈移改变高度相关(r＞0.7,P ＜0.05,P＜0.01).结论 LA可通过显著抑制KM所致磷酸化p38 MAPK的高表达,从而有效拮抗KM的耳毒性,这可能是LA发挥防护作用的分子机制之一.