Department of Otolaryngology-Head and Neck Surgery, Ehime University, Ehime, Japan.
Otol Neurotol. 2011 Dec;32(9):1422-7. doi: 10.1097/MAO.0b013e3182355658.
AM-111, a cell-permeable peptide inhibitor of c-Jun N-terminal kinase, was investigated for its protective effects against ischemic damage of the cochlea in gerbils.
Transient cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for l5 minutes. Then, 10 μl of AM-111 at a concentration of l, 10, or 100 μM in hyaluronic acid gel formulation was applied onto the round window 30 minutes after the insult. Gel without active substance was used in a control group. Treatment effects were evaluated by auditory brainstem response (ABR) and histology of the inner ear.
In controls, transient cochlear ischemia caused a 25.0 ± 5.0 dB increase in the ABR threshold at 8 kHz and a decrease of 13.3 ± 2.3% in inner hair cells at the basal turn on Day 7. Ischemic damage was mild at 2 and 4 kHz. When the animals were treated with AM-111 at 100 μM, cochlear damage was significantly reduced: the increase in ABR threshold was 3.3 ± 2.4 dB at 8 kHz, and the inner hair cell loss was 3.1 ± 0.6% at the basal turn on Day 7. The effects of AM-111 were concentration dependent: 100 μM was more effective than 1 or 10 μM.
Direct application of AM-111 in gel formulation on the round window was effective in preventing acute hearing loss because of transient cochlear ischemia.
细胞渗透型 c-Jun N 末端激酶抑制剂 AM-111 用于研究其对沙土鼠耳蜗缺血性损伤的保护作用。
通过阻塞双侧椎动脉 15 分钟，在动物中引入短暂性耳蜗缺血。然后，在损伤后 30 分钟，将 10 μl 浓度为 1、10 或 100 μM 的 AM-111 置于透明质酸凝胶制剂中，滴注至圆窗。在对照组中使用不含活性物质的凝胶。通过听觉脑干反应（ABR）和内耳组织学评估治疗效果。
在对照组中，短暂性耳蜗缺血导致 ABR 阈值在 8 kHz 时增加 25.0±5.0 dB，第 7 天基底回内毛细胞减少 13.3±2.3%。2 kHz 和 4 kHz 时的缺血损伤较轻。当动物用 100 μM 的 AM-111 治疗时，耳蜗损伤明显减轻：ABR 阈值在 8 kHz 时增加 3.3±2.4 dB，第 7 天基底回内毛细胞丢失 3.1±0.6%。AM-111 的作用呈浓度依赖性：100 μM 比 1 μM 或 10 μM 更有效。
AM-111 通过圆窗直接凝胶给药，对短暂性耳蜗缺血引起的急性听力损失有效。
