CAJ | 학술논문

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 500 mg/kg ，30分钟后再经腹腔注射Fur 0．2 ml/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。
목적：관찰류산잡나매소（kanamycin sulfate ，KM ）여부새미（furosemide ，Fur）연합용약건립약물성쾌속치롱대서동물모형적효과。방법32지SD대서수궤분위A조（KM＋Fur후1천조）、B조（KM＋Fur후7천조）、C조（KM＋Fur후14천조）、D조（대조조），매조8지동물。A、B、C삼조분별경일차성복강주사KM 500 mg/kg ，30분종후재경복강주사Fur 0．2 ml/kg ，공백대조조안체중급여상동제량생리염수。각조재상응적시간점완성은성뇌간반응（auditory brainstem response ，ABR）검측당천，분별행이와기저막포편급소묘전경관찰이와모세포손상정황，면역형광염색관찰라선신경절세포망정황。결과 A、B、C조각빈솔ABR역치교정상대조조명현승고（ P＜0．05）；이A、B、C조각빈솔ABR반응역차이무통계학의의（P＞0．05）。A、B、C조이와저회외모세포명현결실，섬모배렬문란，라선신경절세포적반광안산천동안산단백매-3（cleaved caspase -3）적표체량교정상대조조균명현증가（P＜0．05）。결론류산잡나매소화부새미연합단차복강용약24소시후대서 ABR반응역명현증고，병가견이와저회모세포적명현결실，KM＋Fur연합응용시간단、쾌속이유효적대서이롱동물모형건모방법。
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 an-other intraperitoneal injection of furosemide (Fur ,0 .2 ml/kg ) 30 minutes later .While ,rats in control group D re-ceived same doses of normal saline .Auditory brain responses (ABRs) were recorded at 1 ,7 and 14 day after the in-jections ,which were group A ,group B and group C ,respectively .Hair cell loss ,the spiral ganglions and microstruc-ture 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 obvi-ous 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) .Conclusion 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 .