Sergi Bruno, Ferraresi Aldo, Troiani Diana, Paludetti Gaetano, Fetoni Anna Rita
Institute of Otolaryngology, Catholic University of Rome, Largo A. Gemelli, I-00168 Rome, Italy.
Hear Res. 2003 Aug;182(1-2):56-64. doi: 10.1016/s0378-5955(03)00142-4.
The aim of the present study was to investigate both vestibular and cochlear cisplatin toxicity. Twelve albino guinea pigs were divided into an experimental (n=8) and a control saline group (n=4) and were treated with cisplatin at a daily dose of 2.5 mg/kg for 6 consecutive days. Vestibular dysfunction was evaluated by computing the gain of the vestibular ocular reflex (VOR) evoked by stimulation in the horizontal (HVOR) and vertical (VVOR) planes. Changes in cochlear function were characterised as compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. The onset of vestibular functional impairment was observed on the third day, although the VOR gain decrease was not significant. The impairment of the vestibular function progressed until the sixth day becoming statistically significant particularly at VVOR mid frequencies of stimulation. At these frequencies both macula and crista ampullaris functions are involved. Concomitantly a progressive auditory threshold shift was observed at all stimulus frequencies. The decline of the auditory function was statistically significant from the third day of treatment and it was more evident at high frequencies. Morphological observations showed a massive loss of outer hair cells and a degeneration of the organ of Corti in the basal/middle turns and only a slight loss of hair cells of the cristae ampullares and maculae. In conclusion, functional and morphological data provide evidence that the toxic effect of cisplatin is more pronounced in the organ of Corti than in the vestibular epithelium.
本研究的目的是调查顺铂对前庭和耳蜗的毒性。将12只白化豚鼠分为实验组（n = 8）和对照生理盐水组（n = 4），并以每日2.5 mg/kg的剂量连续6天给予顺铂治疗。通过计算水平（HVOR）和垂直（VVOR）平面刺激诱发的前庭眼反射（VOR）增益来评估前庭功能障碍。耳蜗功能的变化表现为复合动作电位阈值偏移。功能测试后，取出鼓泡并进行处理，以对感觉神经上皮进行形态学检查。尽管VOR增益降低不显著，但在第三天观察到前庭功能损害的开始。前庭功能损害持续进展直至第六天，变得具有统计学意义，尤其是在VVOR刺激的中频。在这些频率下，黄斑和壶腹嵴的功能均受累。同时，在所有刺激频率下均观察到渐进性听觉阈值偏移。从治疗第三天起，听觉功能下降具有统计学意义，且在高频时更为明显。形态学观察显示，外毛细胞大量丢失，基底/中回的柯蒂氏器变性，而壶腹嵴和黄斑的毛细胞仅有轻微丢失。总之，功能和形态学数据提供了证据，表明顺铂的毒性作用在柯蒂氏器中比在前庭上皮中更为明显。
