蝙蝠耳蜗毛细胞损害后支持细胞转分化为再生毛细胞研究  被引量:5

Cochlear supporting cells can transdifferentiate into hair cells after gentamycin toxicity in bats

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作  者:李胜利[1,2] 张正民[3] 张少强[4] 刘思伟[4] 赵谦[4] 闫利英[4] 朱宏亮[2] 

机构地区:[1]西安交通大学医学院第二附属医院研科实验中心,西安710004 [2]西安交通大学神经科学研究中心,西安710061 [3]西安交通大学医学院第二附属医院耳鼻咽喉-头颈外科,西安710004 [4]西安交通大学医学院第一附属医院耳鼻咽喉-头颈外科,西安710061

出  处:《中华耳科学杂志》2010年第3期335-347,共13页Chinese Journal of Otology

基  金:国家自然科学基金项目(编号39970785)

摘  要:目的为探讨哺乳类动物耳蜗毛细胞再生能力的存在和机制,我们选用蝙蝠为动物模型,观察庆大霉素损害耳蜗后毛细胞自发修复再生能力和现象。方法给蹄蝠连续注射庆大霉素10和14天,造成耳蜗毛细胞损害消失。在注射停后、恢复20和40天分别测定ABR反应阈值,并对耳蜗标本进行扫描和透射电镜观察。结果庆大霉素造成蝙蝠耳蜗毛细胞损害消失,ABR反应阈值升高。恢复20和40天后,蝙蝠耳蜗受损的毛细胞部位支持细胞顶表面长出微绒毛,微绒毛发育成纤毛,替补消失的毛细胞,同时伴随有听功能的恢复。结论蝙蝠耳蜗毛细胞损害后支持细胞直接转化为新生的毛细胞,证明蝙蝠耳蜗毛细胞具有再生能力,本研究为哺乳类耳蜗毛细胞再生提供了动物模型。Objective This study investigated the recovery of morphology and functionality of outer hair cells (OHC) in the bat cochlea after gentamicin exposure. Methods Bats received a daily dose of gentamicin for 15 consecu-tive days followed by auditory brainstem response (ABR) assessment on day 16. From day 16 to day 40 of this recovery phase, animals were observed for behavioral responses to sound. On day 40, each bat was again assessed by ABR which demonstrated recovery of some auditory function prior to euthanization for cochlear hair cell examination by scanning elec-tron microscopy(SEM) and transmission electron microscopy (TEM). Results Normally, stereocilia bundles of the OHCs are extensively fused; however, after gentamicin exposure for 10 to 15 days, the OHC body exhibited a dysmorphosis, and there was an absence of neighboring Deiters' cells. More importantly, in the animals allowed to recover from drug expo-sure, we observed normal morphology and functionality of the OHCs with restoration of normal hearing. We also found evidence of bat cochlear Deiters' cells replacing lost hair cells and transdifferentiating into hair cells. This is the first in vivo induction of new hair cells from Deiters' cells in the mammalian cochlea and the first in vivo observation of bat cochlear Deiters' cells undergoing the transdifferentiation process followed by engraftment to the cuticular plate. Conclusion We conclude that in bats, given sufficient drug-free recovery time, cochlear supporting cells can directly transdifferentiate into OHCs after aminoglycoside exposure. This transdifferentiation process is essential for recovery and normal functionality of the OHCs after gentamicin treatment.

关 键 词:外毛细胞 再生 耳蜗 支持细胞 蝙蝠 听功能恢复 

分 类 号:R339.16[医药卫生—人体生理学] R339.37[医药卫生—基础医学]

 

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