中文摘要：

目的观察氨基糖甙类药物庆大霉素进入小鼠肾脏和耳蜗毛细胞在时间和数量上的特点及肾功能和听功能损害情况。方法将18只6周龄的C57小鼠随机分为3组,分别为对照组（contr）、用药后1天组（d1）、用药后7天组（d7）,每组6只动物。置备完成的Texas Red标记庆大霉素（GTTR）以100mg/kg浓度腹腔注射小鼠,1次/天,通过激光共聚焦显微镜观察荧光标记庆大霉素在各组小鼠耳蜗毛细胞和肾脏组织积蓄情况,采用Image-Pro Plus软件测算标本荧光强度值,并进一步估算各标本庆大霉素摄取情况。同时,通过生化检测和听力检测,观察用药后小鼠肾功能和听功能损害情况。结果小鼠标本荧光强度（OD）值测算结果：用药后1天,小鼠肾脏组织中庆大霉素即达到了高水平,P〈0.01;与此同时,小鼠耳蜗毛细胞内虽然检测到明显的红色荧光,但是其OD值要明显低于肾脏组织。用药后7天,肾脏组织和耳蜗毛细胞的OD值均比对照组有极为显著的升高（P〈0.01）。对小鼠肾功能和听力的检测显示,用药后1天小鼠血液中BUN和Scr水平即有明显升高,表明此时肾功能已受到损害;而用药后1天小鼠ABR阈值和对照组相比却未见显著升高（P〉0.05）,表明此时听力损害尚未显现。在用药后7天,小鼠BUN、Scr和ABR阈值水平和对照组相比均有显著改变（P〈0.01）。结论和肾功能损害相比,庆大霉素对小鼠听觉损害具有时间上的滞后效应,而这种时间上的延迟反应为听力损害的临床干预提供了可能。

英文摘要：

Objective To explore time and quantity properties of Texas Red labeling gentamicin entry into renal tissue and cochlear hair cells in mice,as well as secondary renal injury and hearing loss.Methods 18 adult C57 mice（6wks old） were randomly divided into three groups.Two groups received daily intraperitoneal injection of gentamicin labeled with Texas Red at 100 mg/kg for 1 and 7days,respectively.The third group only received the same volume of0.9% saline for control.Laser confocal observations combined with Image-Pro Plus software were employed to estimate time and quantity of uptake gentamicin in both renal tissue and cochlear hair cells.Further,BUN,Scr,and auditory brainstem responses（ABR） threshold were examined to estimate the functional state of kidney and cochlea after gentamicin exposure.Results Significant increase of OD value at d1 was found in renal tissue compared with that of control（P〈0.01）;Significant,but lower increase of OD value at d1 was identified in cochlear hair cells compared with control（P〈0.05）;Similar remarkable enhancement of OD were found at d7 in both renal tissue and cochlear hair cells.Moreover,significant increase of BUN and Scr were detected at d1（P〈0.05）,however,no significant ABR（click） threshold elevation was found at d1 after treatment（P〈0.05）.Dramatic increases of BUN,Scr,and ABR threshold have been found at d7 compared with controls（P0.01）.Conclusions Aminoglycoside induced hearing impairment showed delay reaction compared with aminoglycoside induced rapid injury in renal tissue.The time delay may provide a possibility of clinical invention for aminoglycoside induced hearing loss.