甲磺酸去铁胺抗丁胺卡那霉素耳毒性作用及机理研究

Deferoxamine protects against amikacin ototoxicity and ist mechanism

目的验证铁离子螯合剂甲磺酸去铁胺(deferoxamine mesylate,DFO)抗丁胺卡那霉素耳毒性作用及其机理研究。方法豚鼠随机分为丁胺卡那霉素组(卡那组)、DFO+丁胺卡那霉素组(卡那+DFO组)、对照组,每组8只动物,采用畸变产物耳声发射(DPOAE)、耳蜗铺片及透射电镜、扫描电镜技术,观察用药前后功能和形态学的改变,检测血清中总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-PX)以及丙二醛(MDA)的活力。结果卡那组与卡那+DFO组的DPOAE的幅值有显著性差异(P<0.01),形态学改变与听力改变相平行。DFO组血清中的T-SOD和GSH-PX的活力明显高于卡那组(P<0.05),卡那+DFO组血清中MDA的活力明显低于卡那组(P<0.05)。结论DFO能有效的保护耳蜗免受丁胺卡那霉素的耳毒性侵害,保护作用与自由基相关。

Objective To study the preventin of amikacin ototoxicity by use of deferoxamine （DFO） in guinea pigs. Methods Guinea pigs were randomly assigned to one of three groups： amikacin-treated alone, amikacin and DFO in combination and a control group. Distortion product acoustic emission （DPOAE）, surface preparation technique and transmission and scanning electron microscopy were utilized to evaluate the auditory founction and the cochlear morphology. To explore the mechanism associated with deferoxamie protection, serum activities of T-SOD, GSH-PX and MDA were measured. Results The DPOAE amplitudes of the DFO group and the amikacin group were significantly different（P 〈 0.01 ）. Morphological changes were consistent with founctional changes. Serum activity of T-SOD and GSHPX in the DFO group was much higher than that in the amikacin group（P〈 0.05）, while the serum activity of MDA in the DFO group was significantly lower than that in the amikacin group （P 〈 0.05 ）. Conclusion This study suggests that DFO can reduce amikacin ototoxicity effectively, and the protection mechanism is relevant to free radical scavenging.