依布硒啉对丁胺卡那霉素致豚鼠耳蜗毒性保护作用的实验研究  

The Effects of Ebselen in Prevention of Guinea Pigs against Amikacin-induced Cochlea Damage

作　　者：赵晨[1] 杨宁[1] 李巍[1] 赵宁[1] 惠莲[1] 姜学钧[1] 

机构地区：[1]中国医科大学附属第一医院耳鼻咽喉科,沈阳110001

出　　处：《听力学及言语疾病杂志》2008年第3期213-217,共5页Journal of Audiology and Speech Pathology

摘　　要：目的研究依布硒啉预防丁胺卡那霉素所致豚鼠耳蜗毒性的效果和机制。方法将24只豚鼠随机分为三组,每组8只。丁胺卡那霉素组:丁胺卡那霉素400mg·kg-1·d-1肌肉注射,连续7天;丁胺卡那霉素+依布硒啉组:依布硒啉30mg·kg-1·d-1肌肉注射,30分钟后予丁胺卡那霉素400mg·kg-1·d-1肌肉注射,连续7天;对照组:生理盐水等容量肌肉注射,连续7天。首次用药前1天和7天后分别行双耳畸变产物耳声发射检测,并检测给药后豚鼠血清总超氧化物歧化酶(total superoxide disumutase,T-SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)活性及丙二醛(malondialdhyde,MDA)含量;取左耳蜗行基底膜光镜铺片,右耳蜗行毛细胞扫描电镜及透射电镜观察。结果①光镜及电镜观察显示丁胺卡那霉素组豚鼠用药后,耳蜗大部分毛细胞纤毛缺失、紊乱、粘连,细胞器肿胀,细胞内空泡形成,核膜内陷皱缩;丁胺卡那霉素+依布硒啉组毛细胞纤毛仅轻微粘连,细胞器无肿胀,核膜完整。对照组耳蜗毛细胞未见异常;②丁胺卡那霉素组用药后1、2、4、8kHz的DPOAE幅值显著下降,丁胺卡那霉素+依布硒啉组2、4、8kHz频率处的DPOAE幅值亦出现下降,但幅度小于丁胺卡那霉素组(P<0.01);③丁胺卡那霉素组用药后血清T-SOD、GSH-PX活性显著降低,MDA含量显著增高(P<0.01);丁胺卡那霉素+依布硒啉组血清T-SOD、GSH-PX活性及MDA含量变化程度均轻于丁胺卡那霉素组(P<0.01)。结论依布硒啉在一定程度上可以有效地预防性减轻丁胺卡那霉素所致的耳蜗损伤,其机制可能与其清除活性氧物质、减少氧化应激反应的发生有关。Objective To observe the effects and the mechanism of ebselen （glutathione peroxidase mimic compound）in protecting against the ototoxicity of amikacin. Methods Twenty four guinea pigs were randomly divided into the amikacin group,the amikacin＋ebselen group and the control group. Animals in amikacin group received amikacin（400 mg · kg^-1 · d^-1） , amikacin＋ebselen group received ebselen（30 mg · kg^-1 · d^-1） 30 minutes later after amikacin injection. The control group received saline 7 days. Distortion product otoacoustic emission（DPOAE） was administered on the first day and the eighth day. Hair cells were observed by light scanning electronic microscopic（SEM） and transmission electron microscopic （TEM） after treatment. Total serum superoxide dismutase（T-- SOD） activity,glutathione peroxidase（GSH--PX） activity and malondialdehyde（MDA）content were detected. Results Light microscopic SEM and TEM examination showed that hair cells began with disarray, degeneration and death,but the damage of hair cells was less severe in the amikacin ＋ebselen group than that in the amikacin group. In amikacin group, the DPOAE amplitudes of post--injection decreased and the amplitudes of post--injection also decreased compare to those of post--injection in amikacin＋ ebselen group（P〈0.01）. Serum T--SOD and GSH--PX activity were lower and MDA content was higher in the amikacin group than those in other groups（P〈0.01）. Conclusion Ebselen can effectively reduce the effects of ototoxicity caused by amikacin to a certain degree. The mechanism may be explained by the fact that ebselen can reduce ROS and relieve oxidative response caused by amikacin.

关 键 词：依布硒啉 丁胺卡那霉素 耳毒性 毛细胞 

分 类 号：R764.3[医药卫生—耳鼻咽喉科]