还原型谷胱甘肽对丁胺卡那霉素致豚鼠耳毒性作用的影响

目的：观察还原型谷胱甘肽（GSH）对丁胺卡那霉素耳蜗毒性的干预效果。方法：健康杂色豚鼠56只,随机分为4组,分别肌注丁胺卡那霉素（amikacin）、GSH、Amikacin＋GSH（联合用药）及生理盐水。各组动物在观察期结束后,检测耳蜗组织的活性氧（ROS）水平及谷胱甘肽过氧化物酶（GSH-Px）、超氧化物岐化酶（SOD）、过氧化氢酶（CAT）活力;采用耳蜗基底膜铺片的方法,对深染的外毛细胞表皮板进行计数;扫描电镜观察外毛细胞细胞器的变化。结果：丁胺卡那霉素组ROS水平增高,SOD、CAT、GSH-Px活力降低（P〈0.05）。其余3组的ROS水平均显著低于丁胺卡那霉素组（P〈0.05）,SOD、CAT、GSH-Px活力显著高于丁胺卡那霉素组（P〈0.05）,3组之间的比较各指标均无统计学意义（P〉0.05）。光镜下GSH组耳蜗三排外毛细胞呈v字型排列有序。丁胺卡那霉素组外毛细胞纤毛散乱、倒伏,深染的表皮板数明显增加,联合用药组深染的表皮板数较丁胺卡那霉素组明显减少（P〈0.01）,GSH组与生理盐水组差异无统计学意义（P〉0.05）。电镜下丁胺卡那霉素组核固缩,线粒体数量减少或大多数线粒体空泡变性;GSH组和生理盐水组细胞结构基本正常;联合用药组线粒体染色较深或轻度水肿。结论：GSH与丁胺卡那霉素联合应用可以显著地减轻丁胺卡那霉素的耳毒性。

Effects of reduced glutathione hormone against ototoxicity of amikacin in guinea pigs

AIM :To observe the protective effects of reduced glutathione hormone(GSH)against ototoxicity of amikacin in guinea pigs.METHODS :56 adult guinea pigs were divided into four groups randomly:amikacin group,GSH group,combination group and sodium chloride group.Each group was intramuscularly injected with amikacin,GSH,amikacin GSH and sodium chloride respectively.After the observation,the activities of reactive oxygen species(ROS),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and catalase(CAT)were measured.The number of deeply stained cuticular plate was counted with surface preparation technique of the cochlea.The change of cell organ of outer hair cells was monitored by scanning electron microscope.RESULTS :The activities of SOD,CAT and GSH-Px were significantly decreased and the content of ROS was increased in amikacin group(P < 0.05).However,GSH could significantly inhibit these changes among the animals in treating group.Outer hair cells of GSH group were arranged tidily in three rows and showed characteristic V-arranged stereocilia.Stereocilia of outer hair cells in amikacin group failed off markedly in a disarranged pattern and the number of deeply stained cuticular plate increased significantly.In combination group,the changes of the number of deeply stained cuticular plate showed significant difference as compared with those in amikacin group(P < 0.01).In GSH group and combination group showed no significant difference.In amikacin group,the phenomenon of karyopyknosis appeared,the quantity of mitochondrion decreased and most of them had vacuolar degenerated.The cells of GSH group and sodium chloride group changed slightly.The mitochondrion in combination group was deeply stained and light swelling.CONCLUSION :These results suggest that co-administration of GSH and amikacin can attenuate the ototoxicity of amikacin.