庆大霉素中毒后豚鼠耳蜗毛细胞的再生(英文)

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背景:以往一直认为损伤的毛细胞不具有修复能力。近年研究表明,哺乳动物前庭毛细胞破坏后也保持一定的修复能力。那么,哺乳类动物耳蜗毛细胞破坏后是否具有再生能力?目的:应用扫描电镜技术并结合听性脑干反应测试,观察庆大霉素中毒后不同时间豚鼠耳蜗毛细胞情况和听性脑干反应阈值变化,以观察哺乳动物耳蜗毛细胞受损后能否再生。设计:随机对照动物实验。单位:沈阳医学院生理教研室。材料:实验于2001-11/2002-05在中国医科大学听力研究室完成。选用清洁级耳郭反射灵敏的健康成年白色红目豚鼠60只,随机分为庆大霉素组、正常对照组,每组30只。方法:庆大霉素组每日腹腔注射庆大霉素100mg/kg。正常对照组每日腹腔注射与庆大霉素等量的生理盐水2.5mL/kg,各组皆连续用药10d。每日测量体质量调整药量。在用药前和停药后1,3,30d分别检测听性脑干反应阈值;停药处死后应用扫描电镜技术观察各组豚鼠耳蜗毛细胞情况。主要观察指标:①听性脑干反应阈值。②庆大霉素中毒后不同时间豚鼠耳蜗毛细胞变化。结果:实验动物60只中途无脱落,全部进入结果分析。①庆大霉素组停药后1,3,30d其听性脑干反阈值显著高于正常对照组,差异有显著性[(38.00±3.75),(2.22±3.63)dBnHL,t=30.651,P<0.001];[(39.09±4.22),(2.50±3.54)dBnHL,t=29.708,P<0.001];[(14.50±3.69),(1.50±2.42)dBnHL,t=13.175,P<0.001]。30d时听性脑干反应阈值有明显恢复,但未达到正常水平。②庆大霉素组停药后1d豚鼠耳蜗第二转外毛细胞静纤毛显示融合、扭曲、倒伏、缺失或残缺不全等病理改变,尤其是第三排外毛细胞更为严重,且内毛细胞静纤毛外侧有囊状突出物;停药后3d豚鼠耳蜗第二转外毛细胞静纤毛融合、缺失、倒伏等病理改变仍然存在,内毛细胞静纤毛仍有倒伏现象,而其外侧囊状突出物减少;停药后30d豚鼠耳蜗第二转外毛细胞静纤毛融合、缺失、倒伏等病理改变,明显弱于庆大霉素停药1d和3d,同时耳蜗第三转有新生的静纤毛出现。结论:庆大霉素耳中毒后豚鼠耳蜗毛细胞损伤后存活30d者其耳蜗毛细胞形态上有所恢复,且听性脑干反应阈值也有一定程度的恢复,说明庆大霉素耳中毒后豚鼠耳蜗毛细胞具有再生修复能力。庆大霉素损伤后的毛细胞可以再生。 Background: Hair cells that have been previously considered damaged do not have the ability to repair. Recent studies show that mammalian vestibular hair cells also maintain a certain ability to repair. So, whether mammalian cochlear hair cells have the ability to regenerate after the destruction of the hair cells? Objective: To observe the cochlear hair cells and auditory brainstem response at different time after gentamicin poisoning by scanning electron microscopy and auditory brainstem response Threshold changes in order to observe mammalian cochlea hair cells damaged after regeneration. Design: Randomized controlled animal experiments. Unit: Department of Physiology, Shenyang Medical College. Materials: The experiment was performed at the hearing laboratory of China Medical University from November 2001 to May 2002. A total of 60 healthy red white adult guinea pigs were selected and divided into gentamicin group and normal control group with 30 rats in each group. Methods: Gentamycin group was injected intraperitoneally with gentamicin 100 mg / kg. The normal control group was given intraperitoneal injection of 2.5 mL / kg saline equivalent to gentamicin daily for 10 days. Daily measurement of body mass adjustment dose. The threshold of auditory brainstem response was measured before treatment and at 1, 3 and 30 days after drug withdrawal, and the cochlear hair cells of guinea pigs in each group were observed by scanning electron microscopy after drug withdrawal. MAIN OUTCOME MEASURES: ① Auditory brainstem response threshold. ② gentamicin at different times after cochlear hair cell changes in guinea pigs. Results: There were 60 animals in the experiment without shedding, all of them were involved in the result analysis. ① The anti-thrombosis threshold of the gentamicin group was significantly higher than that of the normal control group at 1, 3 and 30 days after the withdrawal of gentamicin ([38.00 ± 3.75], (2.22 ± 3.63) dBnHL, t = 30.651, P <.001]; [(39.09 ± 4.22), (2.50 ± 3.54) dBnHL, t = 29.708, . At 30 days, the threshold of auditory brainstem response recovered obviously, but did not reach the normal level. (2) The second cochlear outer ciliated cells of cochlear of gentamicin group showed pathological changes of fusion, twisting, lodging, missing or incomplete at 1 day after cessation of administration, especially in the third row of outer hair cells, and the inner hair cells There were cystic protrusions on the outer side of the cilia. After the cessation of treatment, the static cilia fusion, deletion, lodging and other pathological changes still occurred in the second cochlear outer ciliated cells of guinea pigs, The ciliary body cilia, the second cochlear outer hair cell cilia fusion, deletion, lodging and other pathological changes were significantly weaker than gentamicin withdrawal 1d and 3d, at the same time cochlear third turn newborn cilia appear . CONCLUSION: Gentamicin ototoxicity induced cochlear hair cell morphological recovery in guinea pig cochlea hair cells 30 days after injury, and the threshold of auditory brainstem response was also restored to some extent, indicating that guinea pigs after gentamicin ototoxicity Cochlear hair cells have regenerative repair ability. Gentamycin can regenerate hair cells after injury.
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