庆大霉素对水平半规管壶腹嵴的高频旋转感受功能损伤及其形态学基础

High-frequency rotation sensation function damage of the crista of the horizontal semicircular canal induced by gentamicin and its morphological basis

本研究旨在探讨庆大霉素对前庭水平半规管壶腹嵴毛细胞的频率选择性感受功能损伤特点及其形态学基础。以豚鼠为研究对象,给予实验组1、2、3连续每天皮下注射庆大霉素(50mg/kg)1周、2周、3周,对照组皮下注射等量生理盐水。停药后用冰水试验和高频旋转实验诱发并记录视频眼震图(videonystagmography,VNG),用低频和高频旋转实验诱发并记录前庭诱发电位(vestibular evoked potential,VsEP)。视频眼震检查记录眼震持续时间和频率,VsEP检查记录P1、P2波潜伏期和波幅(P1、P2分别起源于前庭神经和前庭神经核)。另将实验组豚鼠分批处死,取水平半规管壶腹嵴标本,扫描、透射电镜观察。结果显示:(1)视频眼震检查:冰水刺激后实验组1、2眼震持续时间和频率与对照组差别无统计学意义(P>0.05),实验组3未引出明显眼震。高频旋转刺激后,与对照组相比,实验组1眼震持续时间和频率无显著差异(P>0.05),而实验组2眼震持续时间缩短和频率下降,差别具有统计学意义(P<0.01);实验组3亦未引出明显眼震。(2)VsEP检查:低频旋转后实验组1、2诱发电位参数与对照组无明显差别(P>0.05),实验组3未见典型波形。高频旋转刺激后,与对照组相比,实验组1的P1,P2无显著差异(P>0.05),而实验组2P1,P2潜伏期延长,两波的波幅均缩短,差异具有统计学意义(P<0.01);实验组3未见典型波形。(3)电镜观察:对照组壶腹嵴毛细胞形态未见异常;实验组1壶腹嵴顶毛细胞纤毛略稀疏,毛细胞水肿;实验组2壶腹嵴毛细胞损伤以中央部分坏死为主,外周细胞形态结构基本完整;实验组3毛细胞纤毛完全消失,未见形态完整毛细胞。以上结果提示,庆大霉素主要影响水平半规管壶腹嵴的高频旋转感受功能,对壶腹嵴毛细胞的损伤先以中央顶部为主,逐渐累及嵴顶外周,直至完全损伤壶腹嵴毛细胞,位于前庭感受器壶腹嵴顶部的毛细胞的损伤和丢失可能是高频旋转感受功能损害和缺失的形态学基础。

The goal of the present study was to explore high-frequency rotation sensation function damage of the crista of the horizontal semicircular canal induced by gentamicin and its morphological basis. The guinea pigs were randomly divided into four groups （group 1, 2, 3 and control group, n=20）. The animals of treated groups received gentamicin subcutaneously （50 mg/kg per day） for 1 week （group 1）, 2 weeks （group 2） and 3 weeks （group 3）, respectively. The animals of control group were administered with equal volume of saline subcutaneously. Videonystagmography （VNG） evoked by ice water or high-frequency rotations, and vestibular evoked potential （VsEP） evoked by low- and high-frequency rotations were recorded after the administration. After VNG and VsEP were examined, the cristae of the horizontal semicircular canals were prepared for scanning and transmission electron microscopy. The results are as follows： （1） In VNG examination, after ice water stimulation, no obvious nystagmus was observed in the animals of group 3, and there was no significant difference in nystagmus frequency and duration among group 1, 2 and control group （P〉0.05）. After high- frequency rotations, no obvious nystagmus was yet observed in the animals of group 3. There were significant differences in the nystagmus frequency and duration of the VNG waves between the experimental group 2 and control group （P〈0.01）, and no difference was found between group 1 and control group （P〉0.05）. （2） In VsEP examination, there was no significant difference in the parameters of VsEP among group 1, 2 and control group （P〉0.05）, and VsEP was not observed in group 3 after low-frequency rotations. After high- frequency rotations, compared with control group, the latencies and amplitudes of P1 and P2 in group 2 significantly decreased （P〈0.01）, while no changes were found in group 1 （P〉0.05）. Group 3 had no response of VsEP to high-frequency rotations. （3） Electron microscopy was used to observe the crista hair cells of the four groups. In control group, the hair cells were normal. In group 1, almost normal appearance with slight edema of the hair cells was shown. In group 2, some hair cells in the central top of the crista necrosed, but other hair cells in the peripheral area showed normal appearance. In group 3, vestibular hair cells were entirely impaired or necrosis. These results show gentamicin selectively induces high-frequency rotation sensation function damage of the crista of the horizontal semicircular canal. The damage is concentrated on the central top area and then subsequently extended to the peripheral area of vestibular crista. It can be inferred that the hair cells in the central top area of the crista are involved in high-frequency rotation vestibular perception.