庆大霉素低剂量预用药降低耳毒性的作用及机制研究  

THE SELF-PROTECTIVE EFFECT OF LOW DOSAGE OF GENTAMICIN

作　　者：亢晓冬[1] 程宁佳[2] 梁国庆[3] 吴培林[1] 虞燕琴[2] 孙霞[4] 

机构地区：[1]杭州师范大学实验动物中心,浙江杭州310036 [2]浙江大学医学院,浙江杭州310058 [3]杭州师范大学环境与生命科学院,浙江杭州310036 [4]杭州师范大学基础医学部,浙江杭州310036

出　　处：《中国应用生理学杂志》2009年第4期561-564,共4页Chinese Journal of Applied Physiology

基　　金：杭州师范大学校级重点课题(2006XMZ05);国家自然科学基金资助项目(30870834)

摘　　要：目的:研究低剂量庆大霉素(GM)预处理对高剂量GM所致耳毒性的保护作用及其机制。方法:豚鼠分为4组:实验对照组、低剂量GM组、低剂量GM预处理组及高剂量GM组。腹腔注射不同剂量的硫酸庆大霉素,每组动物在首次用药前1d及最后1次用药24h后行听性脑干反应(ABR)检测。第二次ABR检测完毕后快速处死动物,取出听泡,测量耳蜗组织NO和MDA含量以及LDH活力。结果:低剂量(10 mg.kg-1.day-1)预处理组ABR反应阈明显低于高剂量组(160 mg.kg-1.day-1,P<0.01)。高剂量组动物耳蜗组织匀浆中NO、MDA含量分别为(15.86±1.976)nmol/mg pro和(19.14±0.9635)nmol/mg pro,明显高于实验对照组、低剂量组和低剂量预处理组(P<0.01)。而低剂量GM预处理后再腹腔注射高剂量GM,能显著降低单独注射高剂量GM引起的耳蜗组织中的NO、MDA的增高(P<0.01)。高剂量组豚鼠耳蜗组织匀浆中LDH活力水平含量明显较实验对照组,低剂量组和低剂量保护组豚鼠增高(P<0.01);低剂量预处理组和低剂量组、实验对照组MDA、NO含量差别不大,各组统计学比较无显著性意义。结论:低剂量GM预处理可降低高剂量GM引起的听力损伤及耳毒性,其保护机制可能与降低了高剂量GM引起的豚鼠耳蜗组织NO、MDA浓度和LDH活力有关。Aim： To approach the protective effect of low dose gentamicin against high ototoxic dose of gentamicin. Methods： The guinea pigs were randomly divided into four groups： control group, low dose group, low dose protective group and high dose group. Each group received multiple intraperitoneal injections of gentamiein sulphate within different duations. Auditory brain stem response （ABR） was examined one day previous to the first and 24 h after the final injection respectively. The bulla was taken out so that the content of NO, MDA and the activity of LDH in cochlear were determined. Results： The threshold of ABR was significantly lower in low dose protective group compared with high dose group （ P 〈 0.01 ）. The content of NO（ 15.86 ± 1.98 nmol/mg pro） and MDA（ 19.14 ±0.96 nmol/mg pro） in homogenate of high dose group was significantly higher than that of control group, low does group and low does protective group（ P 〈 0.01 ）. The increase of the content of NO and MDA induced by high dose GM could be significantly decreased by low dose GM administration previous to high dose injection（ P 〈 0.01 ）. The activity of LDH in homogenate of high dose group was significantly higher compared with control group, low dos group and low dos protective group（ P 〈 0.01）. There was no statistically significant difference of content of NO and MDA among control group, low does group and low does protective group. Conclusion： The protective effects resulting from previous low dose administration to high dose injection of GM may be related to the decrease of content of NO and MDA and activity of LDH both of which induced by high dose GM.

关 键 词：庆大霉素 耳毒性 保护作用 

分 类 号：R331[医药卫生—人体生理学]