卡铂引起的灰鼠耳蜗内毛细胞缺损模式

Carboplatin-induced injury patterns of inner hair cells missing in chinchilla cochlea

目的:研究卡铂损害灰鼠耳蜗内毛细胞(IHCs)的模式,即IHCs何时出现缺损、给药后不同时间基底膜上IHCs缺损的范围、基底膜上IHCs最大缺损部位以及致绝大部分IHCs缺损所需时间等。方法:对成年灰鼠采用一次性卡铂腹腔注射(100mg/kg),给药后不同时间处死动物,常规制备耳蜗铺片和耳蜗图,以定量观察灰鼠耳蜗毛细胞的缺损情况。结果:注射卡铂后从24h～3个月,灰鼠的外毛细胞基本无缺损。IHCs损伤模式的特征:①注射卡铂后24h耳蜗毛细胞完整无损,IHCs从注药后第3天开始出现缺损;②从注射卡铂后3d到3个月期间,IHCs的最大缺损率均出现在第1回和第2回交界处;③IHCs缺损从第1回和第2回交界处开始,范围逐渐向底回和顶回扩展,与顶回相比,底回的IHCs缺损出现早且更严重;④至注射后3个月基底膜上IHCs的缺损呈平坦型。结论:100mg/kg卡铂腹腔注射对各回IHCs的破坏是不均等的,对卡铂的敏感度不一致可能造成了各回IHCs缺损在时间上的差异。

Objective:To explore carboplatin-induced injury patterns of inner hair cells(IHCs) in cochlea of chinchilla, namely, when injury of IHCs occurs, what extension injury of IHCs exists at different time after drug administration, where maximal injury of IHCs locates on basal membrane and how long most IHCs lose after drug administration.Method:Carboplatin of moderate concentration(100 mg/kg) was used to inject peritoneally one time and animals were decapitated on schedule, surface preparations were made and cochleograms were obtained to observe injury of IHCs in the cochleae of chinchillas.Result:Loss of outer hair cells was not observed on basal membrane from 24 hours to 3 months after drug administration except one ear.The characteristic of IHCs injury patterns was found to be: ①IHCs were intact at 24 hours after drug administration.IHCs injury was firstly observed within 3 days.②The maximal rate of IHCs injury located around boundary of turn one and turn two on basal membrane from 24 hours to 3 months.③IHCs injury began from boundary of turn one and turn two and extended to basal turn and apical turn gradually.Compared to apical turn, IHCs injury on basal turn occurred earlier and more severely.④Most IHCs lost in 3 months.Conclusion:Carboplatin of 100 mg/kg unequally destroyed IHCs from different turns.Temporal variance of injury of IHCs from given turn is most likely due to their discrepant sensitivity to carboplatin.