水杨酸钠致耳鸣大鼠下丘GDNF的表达

Expression of GDNF in the Inferior Colliculus of Tinnitus Rats Induced by Sodium Salicylate

周爽;廖华;王文静;杨琨;汪雷;杨希林;

1:武汉大学人民医院耳鼻咽喉头颈外科

摘要

目的探究胶质细胞源性神经营养因子(glial cell-derived neurotrophic factor,GDNF)在慢性注射水杨酸钠致耳鸣大鼠模型下丘中的表达及其在耳鸣发生发展中的作用机制。方法将24只大鼠根据腹腔注射给药方式分为4组,每组6只:对照组(NS组,生理盐水连续注射14天)、急性组(AS组,水杨酸钠200 mg/kg单次注射)、慢性组(SS组,水杨酸钠200 mg/kg连续注射14天,每天2次)、恢复组(RS组,注射方式及时间同慢性组,然后正常喂养14天)。对各组大鼠经上述处理后行听觉惊跳反射前刺激抑制试验(gap-prepulse inhibition of the acoustic startle reflex,GPIAS)检测耳鸣样行为,然后处死并迅速分离下丘,通过蛋白质印迹法(Western blot)检测下丘GNDF及其信号通路RET、P-PI3K p85α、P-AKT蛋白表达量;通过荧光定量PCR(RT-qPCR)检测下丘GDNF、RET、PI3K、AKT1mRNA表达量。结果 4组大鼠中仅SS组大鼠GPIAS值在12和16 kHz明显下降,说明仅SS组大鼠出现耳鸣样行为;Western blot结果显示SS组大鼠下丘GDNF、RET、P-PI3K p85α、P-AKT蛋白表达量较NS组、AS组、RS组均降低(均为P<0.05);RT-qPCR结果显示SS组大鼠下丘GDNF、RET、PI3K、AKT1mRNA表达量较NS组、AS组、RS组均降低(均为P<0.05)。结论慢性注射水杨酸钠致耳鸣大鼠模型下丘GDNF及其介导的GDNF/RET/PI3K/AKT信号通路表达降低,推测GDNF及其信号通路在耳鸣发生发展中有重要作用。

关键词

胶质细胞源性神经营养因子;水杨酸钠;耳鸣;下丘;大鼠

基金项目(Foundation):

国家自然科学基金面上项目（30772397）;; 湖北省自然科学基金面上项目（2015CFB718）

作者

周爽;廖华;王文静;杨琨;汪雷;杨希林;

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