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军事噪声性隐匿性听力损失致小鼠记忆障碍及其海马NR2B机制研究

Memory impairment induced by military noise-induced hidden hearing loss in mice:role of hippocampal NR2B downregulation
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摘要 目的探讨噪声性隐匿性听力损失(NIHHL)发生后是否会导致小鼠记忆功能障碍,并分析记忆相关蛋白N-甲基-D-天冬氨酸受体2A(NR2A)和N-甲基-D-天冬氨酸受体2B(NR2B)在NIHHL小鼠海马区的表达变化。方法采用12只听力正常的雄性C57小鼠,随机分为2组,每组6只。NIHHL组接受110 dB噪声暴露2 h,CON组不予噪声暴露。在噪声暴露前、暴露后1 d和1个月分别进行听性脑干反应(ABR)测试及行为学实验;噪声暴露后1个月,取两组小鼠海马组织和双侧耳蜗组织,采用Western blotting检测海马区NR2A和NR2B蛋白表达,利用免疫荧光染色检测耳蜗带状突触数量。结果与CON组相比,NIHHL组在噪声暴露后1 d听阈升高(P<0.05),ABRⅠ波幅值降低(P<0.01),Ⅰ波潜伏期延长(P<0.05);噪声暴露后1个月,NIHHL组听阈和ABRⅠ波潜伏期恢复至正常水平(P>0.05),但ABRⅠ波幅值仍较低(P<0.05),耳蜗内毛细胞带状突触数量减少(P<0.05)。行为学测试显示:水迷宫中首次抵达原平台位置的潜伏期延长(P<0.01),在目标象限的游泳距离缩短(P<0.05);Y迷宫中自主交替率降低(P<0.01);新物体识别中认知指数降低(P<0.01)。此外,海马区NR2B蛋白表达下调(P<0.05)。结论NIHHL小鼠海马区NR2B蛋白表达下调,可能与其记忆功能障碍的发生发展有关。 Objective To investigate whether noise-induced hidden hearing loss(NIHHL)leads to memory dysfunction in mice and to analyze the expression changes of memory-related proteins N-methyl-D-aspartate receptor 2A(NR2A)and N-methyl-D-aspartate receptor 2B(NR2B)in the hippocampal region of NIHHL mice.Methods A total of 12 male C57 mice with normal hearing were randomly divided into 2 groups,with 6 mice in each group.The NIHHL group was exposed to 110 dB noise for 2 hours,while the CON group received no noise exposure.Auditory brainstem response(ABR)testing and behavioral experiments were conducted before noise exposure,and at 1 d and 1 month after exposure.One month after noise exposure,hippocampal tissues and bilateral cochlear tissues were collected from both groups.Western blotting was used to detect the expression of NR2A and NR2B proteins in the hippocampal region,and immunofluorescence staining was employed to assess the number of cochlear ribbon synapses.Results Compared with the CON group,the NIHHL group showed increased hearing thresholds(P<0.05),decreased ABR waveⅠamplitude(P<0.01),and prolonged ABR waveⅠlatency(P<0.05)at 1 d after noise exposure.At 1 month after noise exposure,the hearing thresholds and ABR waveⅠlatency in the NIHHL group recovered to normal levels(P>0.05),but the ABR waveⅠamplitude remained decreased(P<0.05),and the number of cochlear inner hair cell ribbon synapses was reduced(P<0.05).Behavioral tests revealed prolonged latency to first reach the original platform position in the Morris water maze(P<0.01),shortened swimming distance in the target quadrant(P<0.05);decreased spontaneous alternation rate in the Y maze(P<0.01);and reduced cognitive index in the novel object recognition test(P<0.01).Additionally,the expression of NR2B protein in the hippocampal region was downregulated(P<0.05).Conclusion The downregulation of NR2B protein expression in the hippocampal region of NIHHL mice may be associated with the occurrence and development of memory dysfunction.
作者 付洋 秦建 姜一弘 朱靖 张敏 畅通 王嘉乐 张志纬 陈涛 王小成 FU Yang;QIN Jian;JIANG Yihong;ZHU Jing;ZHANG Min;CHANG Tong;WANG Jiale;ZHANG Zhiwei;CHEN Tao;WANG Xiaocheng(Center of Clinical Aerospace Medicine,School of Aerospace Medicine,Key Laboratory of Aerospace Medicine of Ministry of Education,Air Force Medical University,Xi'an 710032,China;Department of Aviation Medicine,Xijing Hospital,Air Force Medical University,Xi'an 710032,China;No.2 Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China)
出处 《空军军医大学学报》 2026年第1期109-116,共8页 Journal of Air Force Medical University
基金 国家自然科学基金面上项目(82373610) 空军军医大学西京医院创新研究院联合创建项目(LHJJ24KQ04)。
关键词 军事航空噪声 隐匿性听力损失 记忆障碍 听性脑干反应 耳蜗带状突触 海马 NR2A NR2B military aviation noise hidden hearing loss memory impairment auditory brainstem response cochlear ribbon synapses hippocampus NR2A NR2B
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