低剂量顺铂对小鼠耳蜗内毛细胞形态及otoferlin蛋白的影响  

Effect of low dosage of ciplatin on the shape and otoferlin in cochlea inner hair cells

作　　者：孙颖[1] 蒋晓君[1] 陈小宏[1] 袁伟[1] 

机构地区：[1]第三军医大学附属西南医院耳鼻咽喉-头颈外科,重庆400038

出　　处：《临床耳鼻咽喉头颈外科杂志》2014年第11期793-796,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：国家自然科学基金资助项目(No:30973301;81271080);重庆市自然基金资助项目(No:CSTC2009BB5170)

摘　　要：目的:建立稳定有效的低剂量顺铂损伤听觉模型,探讨顺铂造成听功能损伤的机制。方法:将C57小鼠随机分为7组,分别为正常组,不同剂量、不同时间损伤实验组,每组8只。通过小鼠听性脑干反应(ABR)阈值测量、AgNO3毛细胞形态染色、免疫荧光法、RT-PCR测定基膜底回内毛细胞otoferlin蛋白的表达等方式检测顺铂对耳蜗内毛细胞形态及otoferlin蛋白的影响。结果:在同一时间点,用药4d后,1.5mg/kg和3.0mg/kg实验组较正常组小鼠ABR阈值明显升高,用药7d的各实验组ABR阈值较正常组均明显升高。同一剂量下,0.75mg/kg×7d组较0.75mg/kg×4d组阈值明显增高,其余剂量无明显时间差异。实验组中3.0mg/kg实验组蛋白表达均降低,1.5mg/kg实验组与正常组无差异。3.0mg/kg×7d组内毛细胞形态改变最明显,但在各组均未缺失。结论:低剂量顺铂可造成听功能损伤,其损伤机制很可能与内毛细胞的损伤及otoferlin蛋白有关。Objective： To establish the stable and efficient hearing damage model by using low dosage of cispla- tin, and investigate the mechanism. Method： C57 mice were divided into 7 groups （every group, n ： 8）, the first group was the control group, the others were separately intraperitoneally injected with different dosages of cisplatin for different time. We measured the auditory brainstem response（ABR） of the mice, and obtained the basal coil of organ Corti. We observed the shape of inner hair cells（IHC）by staining AgNO3 and marked otoferlin in the IHC by immunofluorescence,successively sliced by laser confocal microscopy. The RNA fragments were amplified by RT-PCR. Result：After cisplatin administration for four days, the thresholds of the ABR improved in 1.5 mg/kg and 3. 0 mg/kg group, and compared with the control group, the ABR thresholds improved in each group with ciplatin administration for seven days. With the same dosage, the ABR threshold of the 0.75 mg/kg × 7 d group was higher than 0.75 mg/kg ×4 d group, and there was no time-effect relationship existing in other groups with different dosage. The otoferlin was less expressed 3.0 mg/kg groups than the control group. However, the otoferlin expressed in the 1.5 rng/kg groups were almost the same as the control group. The alteration of the IHC was observed most rernarkablely in 3.0 mg/kg × 7 d group. Conclusion： Low dosage of cisplatin can impair the hearing, and the expression of otoferlin may involve in the underlying mechanism.

关 键 词：顺铂 内毛细胞 听性脑干反应 

分 类 号：R764[医药卫生—耳鼻咽喉科]