庆大霉素耳毒性模型大鼠耳蜗凋亡诱导因子表达及阿司匹林的拮抗作用

Modification of Aspirin to Expression of AIF in Gentamicin Ototoxicity Model

目的研究庆大霉素耳毒性模型大鼠耳蜗凋亡诱导因子(apoptosis-inducing factor,AIF)表达及阿司匹林的拮抗作用。方法 20只SD大鼠随机分为阿司匹林(acetylsalicylic acid,ASA)+庆大霉素(GM)组(ASA+GM组)和庆大霉素组(GM组),每组各10只动物,GM组腹腔注射GM 120mg·kg-1·d-1,连续21天,ASA+GM组先给予ASA 100mg·kg-1·d-1灌胃,1小时后皮下注射等剂量GM,连续21天;两组动物分别于用药前、用药第7、14、21d行ABR检测,并于用药21d后进行耳蜗毛细胞计数及免疫荧光染色观察两组大鼠耳蜗AIF表达。结果用药第7、14、21dASA+GM组ABR反应阈均低于GM组(P<0.05);用药21d时ASA+GM组耳蜗毛细胞缺失率为7.20%,明显低于GM组(21.51%)(P<0.05),且在两组耳蜗毛细胞亡处均见AIF高表达。结论阿司匹林能拮抗庆大霉素的耳毒性,庆大霉素损伤耳蜗外毛细胞时AIF参与了细胞的凋亡。

Objective To study the expression of apoptosis--inducing factor （AIF） and the antagonism of as- pirin in gentamicin （GM） ototoxicity animal model. Methods Twenty adult SD rats were randomly divided into two groups （ASA and GM in combination, GM-- treated alone）. The count o{ the cochlear hair cells and the auditory brainstem response （ABR） test were used to compare the miss rate and hearing loss after treatment 7 d, 14 d, 21 d. The immunofluorescence staining of cochlear hair cells were used to observe whether AIF mediated cells＂ apoptosis under such circumstances after treatment 21 d. Results Immunofluorescence staining showed that there were apop- totic cochlear hair cells and expression of AIF in both groups. The ABR tests indicated the rats of ASA＋GM group had better hearing than the ones of control group （P〈0.05）. The ASA＋GM group hair cell loss rate was 7.20% and GM group hair cell loss rate was 21.51%. The experimental group had lower miss rate showed by cochlear cells counting （P〈0.05）. Conclusion Cochlear hair cells go through the AIF--mediated apoptosis in the GM ototoxicity animal model. The antagonism of aspirin on the GM ototoxicity is obvious, showing a promising therapeutic agent.