基于斑马鱼模型的4 种氨基糖苷类药物的耳肾毒性比较  

Comparison of Oto-and Renal Toxicities of Four Aminoglycosides in Zebrafish

作　　者：邵微豪 韩雨婕 殷瑜[1] 陈代杰[1] 经莉莉 SHAO Weihao;HAN Yujie;YIN Yu;CHEN Daijie;JING Lili(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200400)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2021年第7期934-939,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金委青年项目(31900099);上海市浦江人才计划(16PJ1405500)。

摘　　要：氨基糖苷类药物的耳肾毒性限制了其临床应用。本研究使用斑马鱼模型评价地贝卡星及其衍生物阿贝卡星、庆大霉素C_(1a)及其衍生物依替米星的胚胎毒性和耳肾毒性。结果表明,4种药物的胚胎致死性大小依次为:阿贝卡星>依替米星>庆大霉素C_(1a)和地贝卡星。肾毒性大小的排序为:地贝卡星>庆大霉素C_(1a)>阿贝卡星>依替米星。毛细胞耳毒性大小的排序依次为:地贝卡星>庆大霉素C_(1a)>阿贝卡星和依替米星。阿贝卡星和依替米星的胚胎致死率高,但在最小致死剂量以下,二者的耳、肾毒性均显著低于先导化合物地贝卡星和庆大霉素C_(1a),并且地贝卡星的耳肾毒性最强。本研究结果同时支持斑马鱼模型可用于氨基糖苷类药物耳肾毒性的快速鉴定。The clinical use of aminoglycoside antibiotics is frequently restricted by their adverse effects to the kidney and inner ears.This study was designed to compare the embryotoxicity,nephrotoxicity and ototoxicity of gentamycin C_(1a),dibekacin and their derivatives(etimicin and arbekacin)in zebrafish embryos.The results demonstrated that the embryonic lethalities for four drugs were in the following order:arbekacin>etimicin>gentamicin C_(1a)and dibekacin.The order of nephrotoxicity was as follows:dibekacin>gentamicin C_(1a)>arbekacin>etimicin.The order of ototoxicity was:dibekacin>gentamicin C_(1a)>arbekacin and etimicin.Arbekacin and etimicin exhibited more developmental toxicities to the young embryos than dibekacin and gentamicin C_(1a).But at sub-minimum lethal doses,arbekacin and etimicin showed significantly reduced toxicities towards kidney and neuromast hair cells,whereas dibekacin had the strongest nephrotoxicity and ototoxicity in zebrafish embryos.Our results also supported that zebrafish could be employed as a convenient and quick platform to evaluate the toxicities of aminoglycoside antibiotics.

关 键 词：胚胎毒性 耳毒性 肾毒性 斑马鱼模型 地贝卡星 阿贝卡星 庆大霉素C_(1a) 依替米星 

分 类 号：R965[医药卫生—药理学]