Activation of caspase-3 Is associated with oxidative stress in the hydropic guinea pig cochlea
Activation of caspase-3 Is associated with oxidative stress in the hydropic guinea pig cochlea
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DOI：
10.1016/j.heares.2004.10.002
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发表时间：
2005-04-01
期刊：
影响因子：
2.8
通讯作者：
Michel, O
中科院分区：
文献类型：
--
作者：
Labbé, D;Teranishi, M;Michel, O
本研究的目的是探讨氧化应激和细胞凋亡在梅尼埃病动物模型中的作用。内淋巴积水(ELH)是梅尼埃病的决定性组织学特征。采用闭合内淋巴管的方法(Kimura‘s法)诱导豚鼠内淋巴积水。假手术的动物作为对照。术后4周，听性脑干反应(ABR)测听结果显示，手术组大鼠听阈明显升高。第二次ABR测量后，立即处死动物进行进一步的免疫组织学检查，用活性caspase-3(CAS-3)的特异性抗体作为细胞凋亡的标志，8-异前列腺素(8-iso)和硝基酪氨酸(NT)的抗体作为氧化应激的指示物。与假手术对照组相比，水化耳蜗肌的螺旋神经节细胞、侧壁的血管和纤维细胞以及Corti器官的支持细胞都显示出强烈的氧化应激标志物的免疫染色。Cas-3在螺旋神经节细胞和侧壁的激活仅见于积水耳蜗区，提示氧化应激参与内淋巴积水的发生发展，并可能导致细胞损伤，通过激活cas-3诱导细胞凋亡。细胞凋亡可能是梅尼埃病后期出现感音神经性听力损失的原因之一。(C)2004爱思唯尔B.V.保留所有权利。
The aim of this study was to investigate the involvement of oxidative stress and apoptosis in an animal model of Meniere's disease. Endolymphatic hydrops (ELH) is generally accepted as the decisive histological characteristic of Meniere's disease.Closure of the endolymphatic duct (Kimura's method) was used to induce endolymphatic hydrops in guinea pigs. Sham-operated animals served as controls. After 4 weeks the animals operated showed a significant elevation of the hearing thresholds as measured by audiometric brainstem responses (ABR) pre- and postoperatively. Immediately after the second ABR measurement, the animals were sacrificed for further immunohistological examinations of the inner ear with specific antibodies to active caspase-3 (cas-3) as a marker for apoptosis and antibodies to 8-isoprostane (8-iso) and nitrotyrosine (NT) as indicators of oxidative stress.Compared with the sham-operated controls, hydropic cochleae showed strong immumostaining for both oxidative stress markers in spiral ganglion cells, in the blood-vessels and fibrocytes of the lateral wall, as well as in supporting cells of the organ of Corti. Activation of cas-3 in spiral ganglion cells and the lateral wall was found exclusively in hydropic cochleae.Our findings suggest that oxidative stress is involved in the development of endolymphatic hydrops and may lead to cellular damage which induces apoptosis by activation of cas-3. Apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of Meniere's disease. (c) 2004 Elsevier B.V. All rights reserved.