硫酸卡那霉素联合呋塞米快速致聋大鼠模型的研究

发布时间：2019-04-02 20:20

【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(P0.05);而A、B、C组各频率ABR反应阈差异无统计学意义(P0.05)。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(P0.05)。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。
[Abstract]:Objective To observe the effect of Kanamycin sulfinate (KM) and furosemide (Fur) on the establishment of an animal model of drug-induced rapid deafness. Methods 32 SD rats were randomly divided into group A (1 day after KM + Fur), group B (7 days after KM + Fur), group C (14 days after KM + Fur), group D (control group), and 8 animals in each group. The three groups of A, B and C were intraperitoneally injected with KM 500 mg/ kg and then injected into the abdominal cavity for 0.2 ml/ kg for 30 minutes, and the blank control group was given the same dose of physiological saline according to the weight. The results of auditory brainstem response (ABR) were performed at the corresponding time points, and the damage of the hair cells of the cochlea was observed by scanning the basal membrane of the cochlea and the scanning electron microscope, respectively, and the apoptosis of the spiral ganglion cells was observed by immunofluorescence staining. Results The ABR threshold in group A, B and C was significantly higher than that in the normal control group (P0.05). The difference of ABR threshold in group A, B and C was not significant (P0.05). The expression of caspase-3 in the spiral ganglion cells increased significantly in the control group (P0.05). Conclusion The response threshold of the ABR in the rat is obviously increased after 24 hours of single intraperitoneal administration of kanamycin and pemide, and the obvious deletion of the back hair cells in the cochlea is found. The combined application of KM + Fur is a simple, rapid and effective model for modeling the rat's deafness.
【作者单位】：第四军医大学西京医院耳鼻咽喉头颈外科;新疆生产建设兵团医院(石河子大学医学院第二附属医院)耳鼻咽喉科;兰州军区临潼疗养院第二疗养区耳鼻咽喉科;
【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
【分类号】：R764.43

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