庆大霉素鼓室内注射后在内耳细胞中的分布  

Distribution of gentamicin in inner ear after intratympanic gentamicin injection

作　　者：刘建平[1] 戴春富[1] 王正敏[1] 迟放鲁[1] 田洁[2] 笪翠弟[2] 

机构地区：[1]复旦大学附属眼耳鼻咽喉科医院耳神经-颅底外科,上海200031 [2]复旦大学附属眼耳鼻咽喉科医院中心实验室,上海200031

出　　处：《中华耳鼻咽喉头颈外科杂志》2006年第11期851-856,共6页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家科委"十五"攻关资助项目(2003BA702B04;2004BA720A18-01);上海市卫生局资助课题(034099);教育部留学回国人员科研启动基金资助项目(2004CFD)

摘　　要：目的观察鼓室内注射庆大霉素后,不同时间庆大霉素在前庭和耳蜗中的分布。方法将庆大霉素同德州红连接形成庆大霉素-德州红耦联物后,行豚鼠鼓室内注射,注射后12h,1、2、3、4、7、14、28d处死动物,Phalloidin染色后运用激光共聚焦扫描显微镜观察基底膜、椭圆囊、球囊、外半规管壶腹嵴庆大霉素分布情况,并进行荧光分布半定量分析。结果庆大霉素自注射后12h起在内耳所有细胞均见分布,在基底膜的外毛细胞、椭圆囊、球囊、外半规管壶腹嵴的感觉细胞聚集明显,主要聚集在毛细胞顶端纤毛下方的细胞质中,支持细胞分布较少。注射后第3天庆大霉素在内耳聚集达到最高峰,并在毛细胞内聚集较长时间。结论庆大霉素-德州红耦联物是一个研究庆大霉素在内耳分布的良好的荧光探针,可用来检测庆大霉素的药代动力学和聚集机制。Objective To investigate uptake and accumulation of gentamicin by cells in the guinea pig inner ear after intratympanic injection using a fluorescent probe gentamicin-Texas-red conjunction （GTTR）. Methods Adult guinea pigs （ n = 80 ） were administered a single dose of GTTR to the middle ear cavity through the intact membrane and survived for 12 h, 24 h, 48 h, 3 d, 4 d, 7 d, 14 d and 28 d. The distribution of GTTR in the cochlear and vestibular ceils was observed after staining with phailoidin-alexa- 488. Texas Red and DMSO were injected into the tympanum as control. Results Diffuse staining of gentamicin in the labyrinth was observed initially after local drug administration. At later time point the outer hair ceils and sensory cells of vestibular organ were staining more densely than the support ceils in the inner ear. The peak level of fluorescent density was reached 3 days after local injection. The GTTR was observed in the infracuticular zone. Conclusions GTTR was a potential fluorescent probe to investigate the pharrnacokinetics and mechanisms of gentamicin accumulation in local application.

关 键 词：庆大霉素类 毛细胞 迷路 药物毒性 

分 类 号：R764[医药卫生—耳鼻咽喉科]