文章摘要
苏波，赖彦冰，王晓迪，褚汉启，冰丹.Nr4a1激动剂胞孢子酮B挽救小鼠噪声性听力损失[J].神经损伤功能重建,2024,(知网首发):
Nr4a1激动剂胞孢子酮B挽救小鼠噪声性听力损失
The Nr4a1 Agonist Cytosporone B Rescues Noise-induced Hearing Loss in Mice
  
DOI：
中文关键词: Nr4a1  Csn-B  噪声性耳聋  氧化应激
英文关键词: nuclear receptor subfamily 4 group A member 1  cytosporone B  noise-induced hearing loss  oxidative stress
基金项目:湖北省重点研发计 划（突发性耳聋预 后预测与精准分型 诊疗智能协同体系 构建，No. 2022BC A006）；武汉市知 识创新专项（婴幼 儿耳聋筛查防治体 系构建及遗传机制 研究，No. 2022022 101015011）；同 济 医院科研基金重点 项目（慢性睡眠剥 夺活化内耳巨噬细 胞经由 NLRP3/IL- 1β/IL1R 导致听力 损失， ）
作者单位
苏波，赖彦冰，王晓迪，褚汉启，冰丹 华中科技大学同济 医学院附属同济医 院耳鼻咽喉-头颈 外科 
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中文摘要:
      目的：探究核受体亚家族4A组成员1（nuclear receptor subfamily 4 group A member 1，Nr4a1）Nr4a1激 动剂胞孢子酮B（cytosporone B，Csn-B）对小鼠噪声暴露后听力损失的治疗作用。方法：采用双氧水刺激 HEI-OC1毛细胞系的方法构建氧化应激细胞模型；通过实时荧光定量PCR（quantitative real-time PCR，qPCR）检测细胞中Nr4a1的mRNA表达水平；分别通过细胞计数试剂盒（cell counting kit-8，CCK8）及流式细胞 术的方法检测细胞活力和细胞凋亡水平以评估Csn-B预处理后经双氧水刺激的细胞状态。构建小鼠噪声 性听力损失模型，运用qPCR和免疫荧光技术检测噪声暴露后Nr4a1在小鼠耳蜗中的表达；通过检测听性脑 干反应（auditory brainstem response，ABR）评估噪声暴露后以及Csn-B连续治疗13 d后小鼠听力情况。结 果：双氧水刺激后HEI-OC1毛细胞中Nr4a1表达上升，细胞活力显著下降，凋亡水平显著升高 ；Csn-B预处 理HEI-OC1毛细胞经双氧水刺激，细胞活力显著高于对照组而凋亡水平则显著低于对照组。在体研究结果 显示，噪声暴露后小鼠听力显著降低，Nr4a1在小鼠耳蜗中的表达水平显著升高。噪声暴露后经Csn-B治疗 小鼠听力得到改善，主要表现为Click-ABR以及Tone Burst-ABR（4 000、8 000Hz处）阈值下降。结论：Nr4a1 激动剂Csn-B增强内耳毛细胞对氧化应激损伤的抵御能力，部分改善噪声暴露后的小鼠听力。
英文摘要:
      To investigate the therapeutic effects of the nuclear receptor subfamily 4 group A member 1(Nr4a1) agonist cytosporone B (Csn-B) on noise-induced hearing loss in mice. Methods: The HEI-OC1 outer hair cell line was subjected to hydrogen peroxide stimulation to establish an oxidative stress cell model. PCR was utilized to assess Nr4a1 expression in the cells. Cell viability was measured using CCK8, and flow cytometry was employed to evaluate apoptosis in cells pre-treated with Csn-B before hydrogen peroxide stimulation. By exposing mice to noisy audio, a model for noise-induced hearing loss was established, and PCR and immunofluorescence techniques were employed to detect Nr4a1 expression in the cochlea following noise exposure. ABR testing was conducted to assess mouse hearing both after noise exposure and following 13 days of continuous Csn-B treatment. Results: Nr4a1 expression increased in HEI-OC1 cells after hydrogen peroxide stimulation, accompanied by a significant decrease in cell viability and an increase in apoptosis. Pre-treatment with Csn-B enhanced cell viability and reduced apoptosis in HEI-OC1 cells exposed to hydrogen peroxide compared to the control group. In vivo studies revealed an increase in Nr4a1 expression in the cochlea of mice after noise exposure, associated with a decline in auditory function. Significant hearing recovery was observed after Csn-B treatment, evidenced by decreased thresholds in Click-ABR and Tone Burst-ABR (at 4000 and 8000Hz). Conclusion: The Nr4a1 agonist Csn-B enhances cellular resilience to oxidative stress and partially rescues noise-induced hearing loss in mice.
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