听觉剥夺及耳蜗内电刺激幼鼠听皮层和下丘核CREB和NMDAR1蛋白表达变化

Variation of CREB and NMDAR1 Proteins Induced by Auditory Deprivation and Intracochlear Electrical Stimulation in Infant Rats

樊碧云;卢振东;程岚;杨军;

1:上海交通大学医学院附属新华医院耳鼻咽喉-头颈外科上海交通大学医学院耳科学研究所

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摘要

目的观察耳聋幼鼠及其耳聋后单耳植入电极电刺激后幼鼠听皮层和下丘核环磷酸腺苷反应元件结合蛋白(cyclic AMP response element-binding protein,CREB)和N-甲基-D-天冬氨酸受体-1(N-methyl-D-aspartic acid receptor one,NMDAR1)表达水平的变化。方法将66只12天龄SD幼鼠随机分为2大组,分别为耳聋造模后4周组(33只)及耳聋造模后6周组(33只)。将耳聋造模后4周组再分为对照1组、耳聋造模后4周组(4周组)及耳聋造模后3周耳蜗内电刺激组1(刺激时间为1周,简称"电刺激1组"),每组11只大鼠;将耳聋造模后6周组再分为对照2组、耳聋造模后6周组(6周组)及耳聋造模后5周耳蜗内电刺激组2(刺激时间为1周,简称"电刺激2组"),每组11只大鼠;对照1、2组均正常饲养。除对照1、2组外,在其余4组幼鼠颈背部、两侧下腹部皮下注射庆大霉素(总量为350mg/kg),半小时后于相同部位注射呋塞米(总量为200mg/kg),两周后行ABR检测,于耳聋造模成功后第3、5周分别对电刺激1、2组的幼鼠植入电极,在耳蜗内进行电刺激,每天3小时,持续7天。于耳聋造模后4、6周分别处死4、6周组大鼠取听皮层和下丘组织,通过免疫组织化学方法,观察CREB和NMDAR1表达水平的变化。结果耳聋造模成功后幼鼠ABR阈值均大于93dB SPL,4周组听皮层、下丘CREB和NMDAR1的表达较对照1组增加,电刺激1组CREB和NMDAR1的表达较4周组增加。6周组听皮层和下丘CREB和NMDAR1的表达较对照2组下降,电刺激2组CREB和NMDAR1的表达较6周组增加。结论听觉剥夺可导致幼鼠听皮层和下丘CREB和NMDAR1早期表达增加而晚期表达下降。耳蜗植入电极电刺激可导致幼鼠听皮层和下丘CREB和NMDAR1的表达增加,反映这两个部位神经元的可塑性变化。

关键词

听觉可塑性;环磷酸腺苷反应元件结合蛋白;N-甲基-D-天冬氨酸受体-1;电刺激;感音神经性聋

基金项目(Foundation):

上海市卫生局项目(2010240);; 上海市科委医学引导项目(114119a6300)联合资助

作者

樊碧云;卢振东;程岚;杨军;

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樊碧云卢振东程岚杨军