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柏柏林通过减少ROS生成和激活PI3K/AKT通路来保护neomycin诱导的耳毒性
Junming Zhang1, Jianhao Song1, Haobo Li1
1College of Biological Science and Medical Engineering, Donghua University, Shanghai, PR China.
Neuroscience letters
|October 16, 2023
概括
柏柏林 (BBR) 通过保护头发细胞和神经元,防止氨基糖化物诱导的听力损失. 这种自身保护剂通过减少氧化应激和激活PI3K/AKT通路而起作用.
科学领域:
- 耳毒性和听力损失研究
- 药理学和药物发现
背景情况:
- 氨基甘氨酸类抗生素会通过损害耳毛细胞 (HCs) 和螺旋质神经元 (SGNs) 来导致无法逆转的听力损失.
- 目前用于治疗耳毒性的治疗方法缺乏适合耳传感表皮的理想治疗剂.
研究的目的:
- 调查柏柏林 (BBR) 作为抗氨基糖化物诱导的耳毒性的耳保护剂的潜力.
- 探索潜在的机制,包括抗氧化性质和涉及的信号通路.
主要方法:
- 科尔蒂器官 (OC) 扩散物的同时处理与新菌素和BBR.
- 评估HC和SGN神经纤维 (NF) 的存活率.
- 测量反应性氧物种 (ROS) 生产和分裂的caspase-3信号.
- 研究PI3K/AKT信号通路,包括使用PI3K/AKT抑制剂 (LY294002).
- 在neomycin受伤的小鼠模型中进行评估.
主要成果:
- 在暴露于neomycin的OC实验体中,BBR显著改善了HC和SGNNF存活率.
- BBR治疗减弱了ROS生成,并减少了分裂的caspase-3信号.
- BBR激活了PI3K/AKT信号,其抑制降低了保护作用.
- 在Neomycin诱导的小鼠耳毒性模型中,BBR的使用保留了HC和SGN.
结论:
- 柏柏林 (BBR) 显示出显著的耳部保护作用,可以防止neomycin诱导的耳部毒性.
- 保护机制涉及通过PI3K/AKT信号通路减轻氧化应激和亡.
- BBR显示出作为一种新型治疗剂的承诺,用于预防由氨基甘油酸抗生素引起的听力损失.
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