Richardson G P, Russell I J
School of Biological Sciences, University of Sussex, Falmer, Brighton, U.K.
Hear Res. 1991 Jun;53(2):293-311. doi: 10.1016/0378-5955(91)90062-e.
Light and electron microscopy have been used to evaluate the effects of treating mouse cochlear cultures with the ototoxic aminoglycoside antibiotic neomycin sulphate at concentrations of 0.2 mM and greater for periods of up to 1 hour. Neomycin rapidly induces the formation of numerous, membrane filled blisters on the apical surfaces of the sensory hair cells. Such morphological damage is restricted to the hair cells, and is not observed on the surfaces of supporting cells within the organ of Corti. Hair cells in apical-coil cultures are less sensitive than those in basal-coil cultures, and, at any given point along the cochlea, outer hair cells appear to be more extensively damaged by neomycin than inner hair cells. These morphological effects of neomycin are considerably more severe when the drug is applied in calcium/magnesium free saline, and can be blocked by elevating the saline concentration of either calcium or magnesium. The effects can also be blocked by lowering the temperature to 4 degrees C, but not by either K+ depolarization or the lectin Concanavalin A. The potential value of this culture system as a model for studying aminoglycoside induced ototoxicity is discussed.
利用光学显微镜和电子显微镜评估了用浓度为0.2 mM及更高的耳毒性氨基糖苷类抗生素硫酸新霉素处理小鼠耳蜗培养物长达1小时的效果。新霉素迅速诱导感觉毛细胞顶端表面形成大量充满膜的水泡。这种形态学损伤仅限于毛细胞，在柯蒂氏器内的支持细胞表面未观察到。顶圈培养物中的毛细胞比底圈培养物中的毛细胞敏感性低，并且在沿耳蜗的任何给定位置，外毛细胞似乎比内毛细胞受到新霉素的损伤更广泛。当在无钙/镁的盐溶液中应用该药物时，新霉素的这些形态学效应要严重得多，并且可以通过提高钙或镁的盐溶液浓度来阻断。这些效应也可以通过将温度降至4摄氏度来阻断，但不能通过K +去极化或凝集素伴刀豆球蛋白A来阻断。讨论了这种培养系统作为研究氨基糖苷类诱导的耳毒性模型的潜在价值。
