多巴胺对豚鼠耳蜗谷氨酸受体NMDA NR_1和NMDA NR_(2A)的调节作用

The Influences of Dopamine on Glutamate Receptor NMDA NR_1 and NMDA NR_(2A) in the Cochlea of Guinea Pigs

侯志强;余力生;李兴启;

1:北京大学人民医院耳鼻咽喉科

2:解放军总医院耳鼻咽喉科研究所

摘要
目的观察豚鼠耳蜗谷氨酸受体NMDA NR1和NMDA NR2A与多巴胺调节作用的相关性,探讨多巴胺在内毛细胞下突触复合体中的作用机制。方法选用杂色豚鼠40只,随机分组,每组10只,分别以右耳行全耳蜗灌流人工外淋巴液和不同浓度的多巴胺,并以人工外淋巴液灌流组的对侧耳蜗作为正常对照组,则共为5组(每组10耳):①正常对照组;②人工外淋巴液组;③10 mmol/L多巴胺组;④30 mmol/L多巴胺组;⑤50 mmol/L多巴胺组。在灌流前、灌流0、1、2 h同时记录各组动物耳蜗电图,应用半定量RT-PCR的方法,观察各组间谷氨酸受体NMDA NR1和NMDA NR2A的mRNA表达量是否有差异。结果多巴胺对豚鼠4 000 Hz耳蜗复合动作电位产生抑制作用,使其阈值升高,且这种抑制作用呈现明显的量效依赖关系。与正常对照组和人工外淋巴液组比较,其余三组谷氨酸受体NMDA NR1的mRNA表达量明显减少(P<0.05),NMDA NR1的表达量与灌流多巴胺的浓度呈现明显的浓度剂量依赖关系;谷氨酸受体NMDA NR2A的mRNA表达量在各组间差异均无统计学意义(P>0.05),随着灌流多巴胺浓度的增加,NMDA NR2A的表达量没有明显变化。结论多巴胺可通过减少谷氨酸受体NMDA NR1的量来实现对听觉通路抑制的作用,而谷氨酸受体NMDA NR2A不参与多巴胺的抑制作用。
关键词
耳蜗;多巴胺;谷氨酸;受体
基金项目(Foundation):
国家自然基金博士点专项基金A966项目(801966);; 国家十一五攻关基金(2007bail8612)
作者
侯志强;余力生;李兴启;
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侯志强余力生李兴启