长期注射水杨酸钠大鼠下丘EphA4的表达

The Expression of EphA4 in Inferior Colliculus Involves in the Pathology of Salicylate Induced Tinnitus in Rat

王文静;杨琨;廖华;杨希林;刘行;

1:武汉大学人民医院耳鼻咽喉头颈外科

摘要
目的通过观察长期水杨酸钠作用后大鼠ABR及下丘EphA4mRNA表达变化,探讨下丘EphA4表达在水杨酸钠耳毒性中的作用。方法将30只健康成年雄性SD大鼠随机分为5组,每组6只:正常对照组(不予任何处理),肌注7天组(肌肉注射水杨酸钠175mg/kg,每天2次,间隔8小时,连续7天),肌注14天组(水杨酸钠用法同前,持续14天),恢复14天组(肌注水杨酸钠14天后,停药恢复14天),恢复28天组(肌注水杨酸钠14天后,停药恢复28天)。对各组大鼠分别于相应时间点进行ABR检测后处死并迅速分离下丘,采用实时荧光定量PCR(real-time PCR)的方法检测各组大鼠下丘中EphA4mRNA表达。结果 1肌注7、14天组大鼠的ABR反应阈分别为38.33±3.73、44.16±1.86dB SPL,较对照组(30.83±1.86dB SPL)明显升高(P<0.05);恢复28天组大鼠的ABR反应阈(32.50±2.50dB SPL)与对照组(30.83±1.86dB SPL)相比,差异无明显统计学意义(P>0.05);2肌注7天组和恢复14天组大鼠下丘EphA4mRNA表达(分别为:0.69±0.11、0.67±0.09)均低于对照组大鼠(0.99±0.01)(均为P<0.05);恢复28天组大鼠下丘EphA4mRNA表达(0.88±0.04)与对照组大鼠比较差异无统计学意义(P>0.05)。结论长期注射水杨酸钠后大鼠下丘的EphA4表达呈可逆性下降,且与水杨酸钠注射后大鼠听功能损伤的变化一致,推测下丘神经元轴突中EphA4参与了水杨酸钠耳毒性的机制。
关键词
水杨酸钠;耳毒性;下丘;EphA4
基金项目(Foundation):
国家自然科学基金青年基金(81100712);; 湖北省自然科学基金面上项目(220100653)资助
作者
王文静;杨琨;廖华;杨希林;刘行;
参考文献

1 Cianfrone G,Pace M,Turchetta R,et al.An updated guide on drugs inducing ototoxicity,tinnitus and vertigo[J].Acta otorhinolaryngologica Italica,2005,25(5Suppl 81):3.

2 Stolzberg D,Chen GD,Allman BL,et al.Salicylate-induced peripheral auditory changes and tonotopic reorganization of auditory cortex[J].Neuroscience,2011,180:157.

3 Cramer KS,Gabriele ML.Axon guidance in the auditory system:multiple functions of Eph receptors[J].Neuroscience,2014,277:152.

4 陈抗松,廖华,杨希林,等.水杨酸钠致耳鸣大鼠的行为学及听性脑干反应改变[J].听力学及言语疾病杂志,2013,21:163.

5 Berger JI,Coomber B,Shackleton TM,et al.A novel behavioural approach to detecting tinnitus in the guinea pig[J].Journal of Neuroscience Methods,2013,213:188.

6 李锦秀,杨琨,吴莎,等.长期注射水杨酸钠对大鼠听皮层酪氨酸受体激酶B及c-fos基因表达的影响[J].听力学及言语疾病杂志,2015,23:276.

7 胡守森,黄治物,吴皓,等.水杨酸盐诱发大鼠听皮层中Egr-1 基因表达的改变[J].听力学及言语疾病杂志,2012,20:561.

8 Hu SS,Mei L,Chen JY,et al.Expression of ImmediateEarly Genes in the Inferior Colliculus and Auditory Cortex in Salicylate-Induced Tinnitus in Rat[J].European Journal of Histochemistry Ejh,2014,58:2294.

9 Chen GD,Kermany MH,D'Elia A,et al.Too much of a good thing:long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity.[J].Hearing Research,2010,265:63.

10 Yu N,Zhu ML,Johnson B,et al.Prestin up-regulation in chronic salicylate(aspirin)administration:an implication of functional dependence of prestin expression.[J].Cellular&Molecular Life Sciences Cmls,2008,65:2407.

11 Cazals Y,Horner KC,Huang ZW.Alterations in average spectrum of cochleoneural activity by long-term salicylate treatment in the guinea pig:aplausible index of tinnitus[J].Journal of Neurophysiology,1998,80:2113.

12 Hu SS,Mei L,Chen JY,et al.Effects of salicylate on the inflammatory genes expression and synaptic ultrastructure in the cochlear nucleus of rats[J].Inflammation,2014,37:365.

13 Berger JI,Coomber B.Tinnitus-related changes in the inferior colliculus[J].Frontiers in Neurology,2015,6:61.

14 Wallace MM,Harris JA,Brubaker DQ,et al.Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem[J].Hearing Research,2016,335:64.

15 Gabriele ML,Brubaker DQ,Chamberlain KA,et al.EphA4and ephrin-B2expression patterns during inferior colliculus projection shaping prior to experience[J].Developmental Neurobiology,2011,71:182.

16 Goldshmit Y,Spanevello MD,Tajouri S,et al.EphA4blockers promote axonal regeneration and functional recovery following spinal cord injury in mice.[J].Plos One,2011,6:e24636.

17 Carmona MA,Pawson AJ.Glial ephrin-A3regulates hippocampal dendritic spine morphology and glutamate transport.[J].Proceedings of the National Academy of Sciences of the United States of America,2009,106:12524.

18 Hollis EN.Axon guidance molecules and neural circuit remodeling after spinal cord injury[J].Neurotherapeutics,2016,13:360.

19 Sheppard A,Hayes SH,Chen GD,et al.Review of salicylate-induced hearing loss,neurotoxicity,tinnitus and neuropathophysiology[J].Acta Otorhinolaryngologica,2014,34:79.

20 尹时华,唐安洲,仁毅,等.水杨酸钠慢性给药对小鼠下丘核神经元超微结构及听反应特性的影响[J].中华耳科学杂志,2007,5:253.

21 何静,蒋斌,梅志刚.中枢神经可塑性变化与耳鸣发生机制研究进展[J].中国全科医学,2014,17:955.

本文信息

PDF(102K)

本文关键词相关文章

水杨酸钠耳毒性下丘EphA4

本文作者相关文章

王文静杨琨廖华杨希林刘行