摘要
目的观察硫酸卡那霉素(kanamycin sulfate,KM)与呋塞米(furosemide,Fur)联合用药建立药物性快速致聋大鼠动物模型的效果。方法 32只SD大鼠随机分为A组(KM+Fur后1天组)、B组(KM+Fur后7天组)、C组(KM+Fur后14天组)、D组(对照组),每组8只动物。A、B、C三组分别经一次性腹腔注射KM 500mg/kg,30分钟后再经腹腔注射Fur 0.2ml/kg,空白对照组按体重给予相同剂量生理盐水。各组在相应的时间点完成听性脑干反应(auditory brainstem response,ABR)检测当天,分别行耳蜗基底膜铺片及扫描电镜观察耳蜗毛细胞损伤情况,免疫荧光染色观察螺旋神经节细胞亡情况。结果 A、B、C组各频率ABR阈值较正常对照组明显升高(P<0.05);而A、B、C组各频率ABR反应阈差异无统计学意义(P>0.05)。A、B、C组耳蜗底回外毛细胞明显缺失,纤毛排列紊乱,螺旋神经节细胞的半胱氨酸天冬氨酸蛋白酶-3(cleaved caspase-3)的表达量较正常对照组均明显增加(P<0.05)。结论硫酸卡那霉素和呋塞米联合单次腹腔用药24小时后大鼠ABR反应阈明显增高,并可见耳蜗底回毛细胞的明显缺失,KM+Fur联合应用是简单、快速而有效的大鼠耳聋动物模型建模方法。
Objective To evaluate the effect of co-administration of the loop diuretic furosemide （Fur） and kanamycin （KM） in the rats in order to establish a reliable animal model of sensorineural hearing loss. Methods Thirty-two Sprague-dawley（SD） rats were randomly divided into 4 groups with 8 rats in each group. Rats in group A,B and C received a single intraperitoneal injection of kanamycin sulfate（KM, 500 mg/kg）, followed by another intraperitoneal injection of furosemide（Fur, 0.2 ml/kg） 30 minutes later. While, rats in control group D received same doses of normal saline. Auditory brain responses （ABRs） were recorded at 1, 7 and 14 day after the injections, which were group A,group B and group C, respectively. Hair cell loss, the spiral ganglions and microstructure were observed by immunofluorescence and scanning electron microscopy. Results The ABR thresholds in group A,B and C were significantly higher than that of in control group D（P〈0.05）. There were no differences of ABR thresholds among group A,B and C（P〉0.05）. Immunofluorescence and scanning electron microscopy showed obvious hair cell loss in the basal turn in each kanamycin groups, with cilia disarrangement and fusion, compared to the same areas, in animals from the control group. The expression of cleaved caspase- 3 significantly increased in each experimental group than that of in the control group（P〈0.05）. Corlclosiorl Co-administration of furosemide and kanamycin intraperitoneally induces profound hearing loss in rats and is an effective method of establishing acute hearing loss model in animal experiments.
出处
《听力学及言语疾病杂志》
CAS
CSCD
北大核心
2014年第3期277-281,共5页
Journal of Audiology and Speech Pathology
基金
国家自然科学基金青年项目(81100713)
国家自然科学基金海外重大合作项目(81120108008)
国家"973"项目课题(2011CB504505)资助
