快速老化小鼠听功能及耳蜗组织中p-ERK1/2的增龄性变化

Degenerative Changes of Auditory Functions and Age-related Expression of p-ERK1/2 in the Cochlea of the Senescence Accelerated Mouse

张红佳;刘强和;王杰;

1:桂林医学院附属医院耳鼻咽喉头颈外科

2:桂林医学院耳鼻咽喉科学研究所

摘要
目的探讨快速老化小鼠的听功能及耳蜗组织中磷酸化的细胞外信号调节激酶1/2(phosphorylated extracellular signal-regulated protein kinases,p-ERK1/2)表达的增龄性变化。方法选用3、5、7月龄的快速老化小鼠亚系8(SAMP8)各6只,分别进行8kHz短纯音听性脑干反应(ABR)检测,并用免疫组化染色方法分别检测各月龄组小鼠耳蜗组织p-ERK1/2的表达,分析其増龄性变化。结果 3、5、7月龄SAMP8小鼠ABR阈值左耳分别为31.817±1.228、54.329±1.459、58.330±1.252dB SPL,右耳分别为32.474±1.041、53.485±1.385、57.842±1.173dB SPL,SAMP8小鼠双耳听性脑干反应阈值随月龄增加而明显提高(P<0.05);3月龄小鼠螺旋神经节细胞、毛细胞中p-EPK1/2平均光密度值分别为0.699 7±0.018 8、0.651 9±0.025 2;5月龄小鼠螺旋神经节细胞、毛细胞中p-EPK1/2平均光密度值分别为0.621 5±0.014 7、0.591 2±0.010 2;7月龄小鼠螺旋神经节细胞、毛细胞中p-EPK1/2平均光密度值分别为0.575 3±0.015 5、0.559 3±0.006 7,p-EPK1/2在不同月龄快速老化小鼠耳蜗组织中的表达光密度值随着月龄增加而显著降低(P<0.05)。结论快速老化小鼠耳蜗组织中p-EPK1/2蛋白的表达水平随着年龄相关性听功能减退而降低,推测p-EPK1/2可能与维持耳蜗功能状态及听觉形成有关。
关键词
快速老化小鼠;听性脑干反应;耳蜗;磷酸化的细胞外信号调节激酶1/2
基金项目(Foundation):
国家自然科学基金项目(81060083)
作者
张红佳;刘强和;王杰;
参考文献

1刘强和,黄鑫,王永宝,等.快速老化小鼠耳蜗组织神经生长因子的增龄性变化[J].中国现代医学杂志,2011,21:3364.

2 刘强和,王永宝,王亮亮,等.神经生长因子在小鼠耳蜗中的表达分布及年龄相关性变化[J].重庆医学,2012,41:2457.

3 王翔,刘强和,王杰.快速老化小鼠听功能及耳蜗组织神经生长因子受体酪氨酸激酶受体A的增龄性变化[J].实用医学杂志,2014,13:2038.

4 Kohno M,Tanimcra S,Ozaki K,Targeting the estracellular signal regulated kinase pathway in cancer thrapy[J].Biol Pharm Bull,2011,34:1781.

5 刘强和,罗香林,耿宛平,等.快速老化小鼠的听功能和耳蜗螺旋神经元的增龄性变化[J].山东大学耳鼻喉眼学报,2008,22:215.

6 刘强和,罗香林,耿宛平,等.快速老化小鼠的听功能和耳蜗毛细胞的增龄性变化[J].华夏医学,2008,21:213.

7 Seidman,MD,Ahmad N,Bai U.Molecular mechanisms of agerelated hearing loss[J].Ageing Res Rev,2002,1:331.

8 Dubno JR,Eckert MA,Lee FS,et al.Classifying human audiometric phenotypes of age-related hearing loss from animal models[J].Journal of the Association for Research in Otolarngology,2013,14:687.

9 Sofroniew MV,Howe CL,Mobley WC.Nerve growth factor signaling,neuropro-tection and neural repair[J].Annu Rev Neurosci,2001,24:1217.

10 Segal RA,Selectivity in neurotrophin signaling:theme and variations[J].Annual Review of Neuroscience,2003,26:299.

11 Roskoski R.ERK1/2MAP kinases:structure,function,and regulation[J].Pharmacological Research,2012,66:105.

12 Shakibaei M,Schulze-Tanzil G,de Souza P,et al.Inhibition of mitogen-activated protein kinase induces apoptosis of human chondrocytes[J].J Biol Chem,2001,276:13289.

13 Boucher MJ,Morisset J,Vachon PH,et al.MEK/ERK signaling pathway regulates the expression of Bcl-2,Bcl-XL,and Mcl-1and promotes survival of human pancreatic cancer cells[J].Journal of Cellular Biochemistry,2000,79:355.

14 Gao F,Hu XY,Xie XJ,et al.Heat shock protein 90protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/AKT and ERK1/2pathways[J].J Zhejiang Univ Sci B,2010,11:608.

15 Zassadowski F,Rochette-Egly C,Chomienne C,et al.Regulation of the transcriptional activity of nuclear receptors by the MEK/ERK1/2 pathway[J].Cellular Signalling,2012,24:2369.