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鼓室注射庆大霉素引起的内耳神经系统继发病变

Secondary neural damage in the inner ear induced by intratympanic gentamicin injection
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摘要 目的对鼓室注射庆大霉素大鼠模型的内耳原发病变和继发损害进行全方位定量评估。方法16只(32耳)成年大鼠被平均分为正常对照组(8耳)、鼓室注射庆大霉素(40 mg/mL)后7 d组(8耳)、鼓室用药后30 d组(8耳)及鼓室用药后60 d组(8耳)。受试大鼠的一侧耳被制作成全内耳膜迷路铺片用以定量评估各个感觉上皮区的毛细胞密度,另一侧耳被制作成颞骨矢状面切片用以定量评估耳蜗和前庭神经元密度及其外周端和中枢端神经纤维的密度。结果对全耳蜗膜迷路铺片的毛细胞定量分析结果显示鼓室注射庆大霉素后各观察时间点的毛细胞损害范围和程度基本相同,说明鼓室注射庆大霉素对毛细胞的一次性破坏没有对存活毛细胞发生明显的继发性破坏作用。对颞骨矢状面切片的内耳神经系统定量分析结果显示,随着鼓室用药后时间的推移,耳蜗和前庭神经元外周端神经纤维在毛细胞死亡后30 d已经消失殆尽,但是内耳神经元的细胞体及其中枢端神经纤维在毛细胞死亡后30 d尚未发生病变,直到毛细胞死亡后60 d,内耳神经元及其中枢端神经纤维才表现出明显的继发性破坏。结论在毛细胞缺失后,内耳神经元外周端神经纤维发生的退化早于内耳神经元细胞体及其中枢端神经纤维的延迟性破坏。外周端神经纤维的早期退化说明内耳神经元与内耳感觉上皮之间的神经联系已经完全丧失,中枢端神经纤维的继发性破坏证明内耳与中枢之间的神经联系彻底中断。 Objective To conduct a comprehensive quantitative evaluation of the primary lesions and secondary damages of the inner ear in the rat model of intratympanic gentamicin injection.Methods Sixteen adult rats were randomly divided into four groups,with 4 rats in each group:a normal control group(8 ears),a group 7 days after single intratympanic injection of gentamicin(40 mg/mL)(8 ears),a group 30 days after single injection of gentamicin(8 ears),and a group 60 days after single injection of gentamicin(8 ears).One ear from each rat was made into flat surface preparation of whole membranous labyrinth to quantitatively evaluate the hair cell density in each sensory epithelial region,while the other ear was sectioned along the sagittal plane of the temporal bone for quantitative evaluation of the density of cochlear and vestibular neurons and the density of their peripheral and central nerve fibers.Results Quantitative analysis of hair cells in the surface preparations of whole membranous labyrinth showed that the extent and severity of hair cell damage were consistent across different observation time points following intratympanic gentamicin injection.This indicated that gentamicin-induced initial destruction of hair cells did not cause significant secondary degeneration of the surviving hair cells.Quantitative analysis of the inner ear nervous system in sagittal temporal bone sections revealed that the peripheral nerve fibers of cochlear and vestibular neurons were almost completely absent 30 days after hair cells death.However,the soma of the inner ear neurons and their central nerve fibers remained unaffected at 30 days after hair cell missing.Significant secondary degeneration of the inner ear neurons and their central nerve fibers did not occur until 60 days after the hair cell loss.Conclusion The degeneration of peripheral nerve fibers of inner ear neurons occurs earlier than the delayed degeneration of neuronal cell bodies and their central nerve fibers after hair cell loss.The early degeneration of peripheral n
作者 丁大连 石林 邢雅智 李鹏 亓卫东 张建辉 蒋海燕 时海波 DING Dalian;SHI Lin;XING Yazhi;LI Peng;QI Weidong;ZHANG Jianhui;JIANG Haiyan;SHI Haibo(Department of Otolaryngology Head and Neck Surgery,the Sixth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China;State University of New York at Buffalo,NY 14214,USA;Department of Otolaryngology Head and Neck Surgery,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;Department of Otolaryngology Head and Neck Surgery,Chengdu Third People’s Hospital,Chengdu 610014,China;Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital,Dalian Medical University,Dalian 116011,China;Department of Otolaryngology Head and Neck Surgery,Huashan Hospital,Fudan University,Shanghai 200040,China)
出处 《中国耳鼻咽喉颅底外科杂志》 CAS CSCD 2024年第6期11-19,共9页 Chinese Journal of Otorhinolaryngology-skull Base Surgery
基金 国家自然科学基金项目(82171147,82071050,81973913) 科技部国家重点研发计划(2023YFC2410205) 四川省自然基金(2023NSFC0621)。
关键词 内耳 毛细胞 神经系统 庆大霉素 延迟性神经元死亡 Inner ear Hair cells Nervous system Gentamicin Delayed neuronal death
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