鸡卡那霉素耳中毒后听功能恢复不全的形态基础

Anatomical Correlation of Permanent Hearing Loss in Chick Inner Ear following Kanamycin Damage

目的 探讨鸡卡那霉素耳中毒后听功能恢复不全的形态基础。方法 将 3天龄罗曼鸡按 2 0 0mg·kg-1·d-1连续肌注卡那霉素 10天 ,分别于施药第 8天、停药后 1、7、15、30、6 0天时处死 ,对照组动物不给予任何药物。动物处死前先用半正弦波 (40 0 0Hz)刺激行ABR检查 ,完毕后取颞骨 ,行扫描电镜标本制作及观察。结果 鸡ABR阈移于施药完毕时达到极限 ,停药后即开始恢复 ,停药后 7天时 ,ABR阈值有明显恢复 ,停药后 15天时 ,其ABR阈值已接近正常 ,但直至停药后 2个月时 ,ABR阈值仍有 15dBSPL未能完全恢复。扫描电镜所见 ,施药完毕时 ,鸡基底乳头近端 4 0 %区域内毛细胞完全破坏消失 ,并见毛细胞再生修复现象 ,停药后 7天时 ,毛细胞形态有成熟 ,其表皮板增大 ,表面静纤毛丛排列成阶梯样 ,停药后 15天时 ,基底乳头损伤区域已基本修复 ,大多数再生毛细胞已基本成熟 ,但直至停药后 2月时其静纤毛丛极向仍未完全恢复正常。结论 鸡卡那霉素耳中毒后 。

Objective To study anatomical correlation of permanent hearing loss in chick inner ear following Kanamycin damage. Methods Newly hatched chicks were given daily injection of kanamycin (200 mg·kg -1 ·d -1 ) for 10 consecutive days. Animals were sacrificed after 8 days and were exposed to drug for a total of 10 days then allowed to survive 1, 7, 15, 30, and 60 days before they were killed. At the end of survival period the auditory brain stem response(ABR) was measured. After ABR measurement, animals were sacrificed immediately and their basilar papillae were studied by scanning electron microscopy.Results ABR measurement showed that the most threshold shifts occurred on the animals at the end of 10 days of kanamycin treatment. The hearing function of animals began to recover in a few days and returned to nearly normal in two weeks after drug cessation. Thresholds measured at 7 days were significantly better than those measured at 1 days after drug cessation ( P <0.01), and again measured at 15 days were better than at 7 days ( P <0.01). A residual 15 dB threshold shift still persisted 60 days after kanamycin ototoxicity, however. Scanning electron microscopy study showed that hair cells degeneration was complete in the basal 40% of the basilar papilla at the end of 10 days of kanamycin administration, and at the same time the embryonic appearing tufts of stereocilia on the regenerated hair cells were clearly visible throughout the region of hair cell loss. In fact, a few newly very small stereociliary bundles already occurred on the basilar papilla at the 8th of kanamycin treatment. Partial hair cell repopulation of the basal tip by regenerated hair cells was seen 7 days after termination of kanamycin administration. These hair cells demonstrated varying degrees of maturity, and stereociliary bundles on the most of regenerated hair cells were staircase organization. At 15 days following last injection hair cell repopulation of the hair cell loss region by regenerated hair cells was completed, and most of regenerated hair cells were mature. The development of stereocilia on regenerated hair cells paralleled the development of cuticular plate, and stereocilia bundle orientation was gradually improved over time. However, the stereocilia bundle orientation was still not normal by 60 days following drug cessation.Conclusion The abnormal stereocilia bundle orientation on regenerated hair cells may be responsible for the permanent hearing loss in the chick inner ear following Kanamycin ototoxicity.