Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs
Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs
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DOI：
10.1016/j.anl.2004.11.006
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发表时间：
2005-03-01
影响因子：
1.7
通讯作者：
Yamashita, H
中科院分区：
文献类型：
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作者：
Okuda, T;Sugahara, K;Yamashita, H
用豚鼠作为动物模型系统，对caspase抑制剂对耳蜗的保护作用进行了体内研究。庆大霉素（12 mg/ml）以0.5 μ l/h的速度通过渗透泵注入豚鼠耳蜗淋巴周围间隙，持续14天。除庆大霉素外，其他动物分别给予一般半胱天冬酶抑制剂z-Val-Ala-Asp (Ome)-氟甲基酮（z-VAD-FMK）或z-Leu-Glu-His-Asp-FMK （z-LEHD-FMK）和半胱天冬酶9抑制剂。在庆大霉素给药后4、7和14天，同时接受z-VAD-FMK和z-LEHD-FMK治疗的动物，听觉脑干反应阈值的升高有所降低。在接受半胱天冬酶抑制剂和庆大霉素治疗的动物中，耳蜗感觉毛细胞存活的数量更多，而只接受庆大霉素治疗的动物的感觉毛细胞则严重受损。这些结果提示庆大霉素诱导的听觉细胞死亡与体内半胱天冬酶的激活密切相关。2004爱思唯尔爱尔兰有限公司版权所有。
The efficacy of caspase inhibitors for protecting the cochlea was evaluated in an in vivo study using guinea pigs, as the animal model system. Gentamicin (12 mg/ml) was delivered via an osmotic pump into the cochlear perilymphatic space of guinea pigs at 0.5 mu l/h for 14 days. Additional animals were given either z-Val-Ala-Asp (Ome)-fluoromethyl ketone (z-VAD-FMK) or z-Leu-Glu-His-Asp-FMK (z-LEHD-FMK), a general caspase inhibitor and a caspase 9 inhibitor, respectively, in addition to gentamicin. The elevation in auditory brain stem response thresholds, at 4, 7, and 14 days following gentamicin administration, were decreased in animals that received both z-VAD-FMK and z-LEHD-FMK. Cochlear sensory hair cells survived in greater numbers in animals that received caspase inhibitors ill addition to gentamicin, whereas sensory hair cells in animals that received gentamicin only were severely damaged. These results suggest that auditory cell death induced by gentamicin is closely related to the activation of caspases in vivo. (c) 2004 Elsevier Ireland Ltd. All rights reserved.