飞机噪声刺激引起小鼠初级听皮层神经元凋亡
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摘要
目的噪声对人体最直接的危害是听力损伤,以往研究多关注外周听觉器官改变,其对听皮层神经元的影响并不清楚,本研究探讨飞机噪声刺激5天后,小鼠初级听皮层神经元的形态改变和凋亡相关变化。方法采用苏木素-伊红(hematoxylin and eosin,HE)染色检测小鼠神经元形态变化,采用免疫组织化学方法和Western blot检测B淋巴细胞瘤-白血病2蛋白(Bcl-2)、Bcl-2相关X蛋白(Bax)、天冬氨酸蛋白水解酶-3(caspase-3)蛋白表达。结果与对照组相比,噪声刺激可导致小鼠初级听皮层神经元体积变小、分布不均、颜色深染、胞浆不清、核固缩。噪声组小鼠听皮层神经元凋亡比例显著增加,Bax蛋白表达显著增加,而Bcl-2表达无明显改变,Bax/Bcl-2显著增加,同时伴有caspase-3水平增加。结论飞机噪声刺激可导致小鼠听皮层神经元形态异常,出现明显凋亡改变,其机制与Bax/Bcl-2信号通路及caspase-3活性增加有关。
Objective The most direct damage caused by noise to human body is hearing loss.Previous researches have paid most of their attention to the changes in peripheral auditory organs,while the effect on auditory cortical neurons is not clear.The present work was designed to investigate the change in the morphology and apoptosis level of mouse primary auditory neurons in cerebral cortex after 5 days' exposure to aircraft noise.Methods The morphological change of the neurons was observed by Hematoxylin and Eosin(HE) staining.Western blot and immunohistochemistry were performed to detect the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax) and Caspase-3.Results Compared to the control group,in the mice exposed to noise,the primary auditory cortical neurons became smaller,unevenly distributed and deeply stained with HE.The cytoplasm was blur and karyopycnosis was observed which worsened with the increase of exposure time.The apoptotic ratio was noticeably higher.The expression of Bax protein increased significantly while that of Bcl-2 showed no obvious change,the ratio of Bax to Bcl-2 thus being much higher.The expression of Caspase-3 protein also increased.Conclusion Stimulation by aircraft noise induces the morphological change and apoptosis of mouse primary auditory cortical neurons.The mechanism might involve the activation of Bax/Bcl-2 pathway and Caspase-3.
Objective The most direct damage caused by noise to human body is hearing loss.Previous researches have paid most of their attention to the changes in peripheral auditory organs,while the effect on auditory cortical neurons is not clear.The present work was designed to investigate the change in the morphology and apoptosis level of mouse primary auditory neurons in cerebral cortex after 5 days' exposure to aircraft noise.Methods The morphological change of the neurons was observed by Hematoxylin and Eosin(HE) staining.Western blot and immunohistochemistry were performed to detect the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax) and Caspase-3.Results Compared to the control group,in the mice exposed to noise,the primary auditory cortical neurons became smaller,unevenly distributed and deeply stained with HE.The cytoplasm was blur and karyopycnosis was observed which worsened with the increase of exposure time.The apoptotic ratio was noticeably higher.The expression of Bax protein increased significantly while that of Bcl-2 showed no obvious change,the ratio of Bax to Bcl-2 thus being much higher.The expression of Caspase-3 protein also increased.Conclusion Stimulation by aircraft noise induces the morphological change and apoptosis of mouse primary auditory cortical neurons.The mechanism might involve the activation of Bax/Bcl-2 pathway and Caspase-3.
引文
[1]李大鹏,张红蕾,郭睿,等.噪声对飞行学员高频听力影响及招收飞行学员体检部分听力标准的探讨.中国眼耳鼻喉科杂志,2015,15(5):331-334.
[2]黄东林,杨敏.飞机噪声对机坪地勤人员听力的影响.中国医药指南,2015,13(9):283.
[3]尹建坤,田瑞丽,李洪波,等.机场周边居民对飞机噪声反应的主观烦恼度研究.绿色科技,2014,(9):218-222.
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[7]薛秋红,何坚,陈佳,等.内质网应激反应参与强噪声诱导豚鼠耳蜗螺旋神经节细胞凋亡的研究.武汉大学学报·医学版,2012,33(2):169-173.
[8]Xiong M,Wang J,Yang C,et al.The cochlea magnesium content is negatively correlated with hearing loss induced by impulse noise.Am J Otolaryngol,2013,34(3):209-215.
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[10]黄河银,刘砚星,徐鸥,等.听觉剥夺后大鼠听皮层神经元的形态学变化和SHP-2基因的表达.听力学及言语疾病杂志,2013,21(5):515-518.
[11]Jaramillo S,Zador AM.The auditory cortex mediates the perceptual effects of acoustic temporal exceptation.Nat neurosci,2010,14(2):246-251.
[12]George P,Keith B.The mouse brain in stereotaxic coordinates.2nd edition.San Diego:Academic Press,2001,21-112
[13]李春光,王转斌,刘军坛.飞机噪声的危害及其防治对策探讨.甘肃科技,2006,22(9):130-132.
[14]吴迪,林炜栋,邱丽君.噪声对警务直升机飞行员听力的影响观察.海军医学杂志,2015,36(4):301301.
[15]曲雁,李云,丁大连.噪声性耳聋的研究进展.河北医科大学学报,2009,30(8):860-864.
[16]Jie Tang,Weiguo Yang,Nobuo Suga.Modulation of thalamic auditory neurons by the primary auditory cortex.J Neurophysiol,2012,108(3):935-942.
[17]任红苗,王宜南,陈继川.年龄相关性听力损失小鼠听皮层神经元凋亡及听功能变化.中华耳科学杂志,2013,11(3):457-460.
[18]李洪波,陈继川,姬长友.C57BL/6J小鼠初级听皮层神经元凋亡与caspase.3表达的年龄相关性改变.听力学及言语疾病杂志,2009,17(3):248-251.
[19]董雅洁,高维娟.bcl-2,bax,caspase-3在细胞凋亡中的作用及其关系.中国老年学杂志,2012,11(32):4828-4830.
[20]Kirsch DG,Doseff A,Chau BN,et al.Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome C mitochondrial cytochrome release.J Biol Chem,1999,274(30):21155-21161.
[2]黄东林,杨敏.飞机噪声对机坪地勤人员听力的影响.中国医药指南,2015,13(9):283.
[3]尹建坤,田瑞丽,李洪波,等.机场周边居民对飞机噪声反应的主观烦恼度研究.绿色科技,2014,(9):218-222.
[4]Henderson D,Bielefeld EC,Harris KC,et al.The role of oxidative stress in noise-induced hearing loss.Ear Hear,2006,27(1):1-19.
[5]Chen YS,Tseng FY,Liu TC,et al.Invovement of nitric pxide generation in noise-induced temporary threshold shift in guinea pigs.Hear Res,2005,203(1-2):94-100.
[6]戴清蕾,薛希均,严旭坤,等.噪声性耳聋相关的细胞病理生理变化概述.中华耳鼻咽喉头颈外科杂志,2014,(7):610-613.
[7]薛秋红,何坚,陈佳,等.内质网应激反应参与强噪声诱导豚鼠耳蜗螺旋神经节细胞凋亡的研究.武汉大学学报·医学版,2012,33(2):169-173.
[8]Xiong M,Wang J,Yang C,et al.The cochlea magnesium content is negatively correlated with hearing loss induced by impulse noise.Am J Otolaryngol,2013,34(3):209-215.
[9]Chen Z,Ulfendahl M,Ruan R,et al.Protection of auditory function against noise trauma with local caroverine administration in guinea pigs.Hear Res,2004,197(1-2):131-136.
[10]黄河银,刘砚星,徐鸥,等.听觉剥夺后大鼠听皮层神经元的形态学变化和SHP-2基因的表达.听力学及言语疾病杂志,2013,21(5):515-518.
[11]Jaramillo S,Zador AM.The auditory cortex mediates the perceptual effects of acoustic temporal exceptation.Nat neurosci,2010,14(2):246-251.
[12]George P,Keith B.The mouse brain in stereotaxic coordinates.2nd edition.San Diego:Academic Press,2001,21-112
[13]李春光,王转斌,刘军坛.飞机噪声的危害及其防治对策探讨.甘肃科技,2006,22(9):130-132.
[14]吴迪,林炜栋,邱丽君.噪声对警务直升机飞行员听力的影响观察.海军医学杂志,2015,36(4):301301.
[15]曲雁,李云,丁大连.噪声性耳聋的研究进展.河北医科大学学报,2009,30(8):860-864.
[16]Jie Tang,Weiguo Yang,Nobuo Suga.Modulation of thalamic auditory neurons by the primary auditory cortex.J Neurophysiol,2012,108(3):935-942.
[17]任红苗,王宜南,陈继川.年龄相关性听力损失小鼠听皮层神经元凋亡及听功能变化.中华耳科学杂志,2013,11(3):457-460.
[18]李洪波,陈继川,姬长友.C57BL/6J小鼠初级听皮层神经元凋亡与caspase.3表达的年龄相关性改变.听力学及言语疾病杂志,2009,17(3):248-251.
[19]董雅洁,高维娟.bcl-2,bax,caspase-3在细胞凋亡中的作用及其关系.中国老年学杂志,2012,11(32):4828-4830.
[20]Kirsch DG,Doseff A,Chau BN,et al.Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome C mitochondrial cytochrome release.J Biol Chem,1999,274(30):21155-21161.