二甲基亚砜对在体耳蜗毛细胞的毒性作用

目的研究二甲基亚砜(DMSO)对在体耳蜗毛细胞的毒性作用。方法取清洁级健康、ABR阈值正常SD大鼠32只,雌雄不限,体重100-120g。随机分成4组,人工外淋巴液对照组(即0%组)8只;0.1%DMSO溶液组8只;1%DMSO溶液组8只;5%DMSO溶液组8只。所有动物均取右耳作为实验耳。通过耳蜗鼓阶打孔显微注射向每个实验耳注入不同浓度DMSO溶液4ul。术前1天和术后7天分别进行ABR(click和toneburst)检测。激光共聚焦显微镜观察DMSO溶液导入7天后的毛细胞变化。结果人工外淋巴液对照组click、4kHz、8kHz、16kHz处阈移平均值均<5dBSPL,仅于32kHz处有约13dBSPL的阈移,形态方面未见明显损伤;0.1%浓度组在click、4kHz、8kHz处阈移平均值均<5dBSPL,而32kHz处阈移约25dBSPL,与人工外淋巴液对照组比较提示有统计学意义,激光共聚焦显微镜观察底回时偶见少数内毛细胞胀大;1%浓度即可引起OHC大量丢失,造成相应纤毛表皮板缺如,且以底回最重,各频率ABR阈移均>15dBSPL,32kHz处阈移>30dBSPL;当浓度增加到5%时,不仅损伤耳蜗底回的外毛细胞,也导致内毛细胞的丢失,所造成的听力损失在32kHz处较1%组严重。结论 DMSO对毛细胞的损伤存在剂量依赖性,损伤程度自耳蜗底回向顶回逐渐减轻。

Cytotoxic effects of dimethyl sulphoxide on cochlear hair cells in vivo

Objective To assess cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear hair cells in vivo. Methods Healthy 4-week-old SD rats (100 - 120 g, n=32) of either sex were randomly divided into four groups to be treated with artificial perilymph (control group) or DMSO at 0.1%, 1% or 5%. Auditory brainstem responses (ABR) were tested 1 day before and 7 days after drug administration to determine its effects on hearing. Changes of cochlear hair cells were examined under a confocal microscope 7 days after drug administration. Results In the control group, ABR threshold shift was < 5 dB in response to clicks and 4, 8 and 16 kHz tone pips,and 13 dB to 32 kHz tone pips. DMSO treatment at 0.1% caused little or no damage. However, at 1% and 5%, DMSO caused considerable loss of OHC with ABR threshold shifts > 15 dB at most frequencies and > 30dB at 32 kHz. At 5%, DMSO caused damage in both outer and inner hair cells. Conclusion DMSO-induced damage appears to be dose-dependent. Hair cell damage caused by DMSO increases towards the basal turn in the cochlea.