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水杨酸钠对大鼠耳蜗螺旋神经节神经元的毒性研究：多巴胺受体介导NMDA受体与GABAA受体的表达

韦廷佳, 陈慧英, 黄喜, 翁敬锦, 覃江圆, 苏纪平^*

广西医科大学第一附属医院耳鼻咽喉头颈外科，南宁 530021

摘要

本研究旨在观察多巴胺受体(dopamine receptor, DR)是否参与水杨酸钠(sodium salicylate, SS)对大鼠耳蜗螺旋神经节神经元(spiral ganglion neuron, SGN) N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor, NMDAR)和A型γ-氨基丁酸受体(γ-aminobutyric acid type A receptor, GABAAR)亚单位蛋白表达的作用。原代培养大鼠SGN，用免疫荧光技术检测SGN上第一家族多巴胺受体(DR1)和第二家族多巴胺受体(DR2)的表达；分别用5 mmol/L SS、SS + DR1拮抗剂(SCH23390, 20 μmol/L)和SS + DR2拮抗剂(Eticlopride, 20 μmol/L)处理SGN后，用Western blot检测NMDA受体NR1亚单位、GABAA受体α2亚单位(GABAA receptor subunit α2, GABRα2)蛋白的表达。结果显示，SGN的胞体与突起均有DR1、DR2表达；SS可下调GABRα2和NR1的膜蛋白表达，但不影响二者的总蛋白表达；SCH23390和Eticlopride均能逆转SS对GABRα2和NR1膜蛋白表达的下调作用。以上结果提示，SS可影响SGN表面GABAAR和NMDAR的转运，其作用机制涉及DR的介导作用。

关键词： 水杨酸钠; 耳蜗螺旋神经节神经元 ; 多巴胺受体 ; N-甲基-D-天冬氨酸受体 ; A型γ-氨基丁酸受体

分类号：R764.4

A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAA receptors

WEI Ting-Jia, CHE Hui-Ying, HUANG Xi, WENG Jing-Jin, QIN Jiang-Yuan, SU Ji-Ping^*

Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

Abstract

The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABAA and NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.

Key words: sodium salicylate; spiral ganglion neurons ; dopamine receptor ; NMDA receptor ; GABAA receptor

收稿日期：2016-09-21　　录用日期：2017-03-24

通讯作者：苏纪平　　E-mail: ymsu2@126.com

引用本文：

韦廷佳, 陈慧英, 黄喜, 翁敬锦, 覃江圆, 苏纪平. 水杨酸钠对大鼠耳蜗螺旋神经节神经元的毒性研究：多巴胺受体介导NMDA受体与GABAA受体的表达[J]. 生理学报 2017; 69 (3): 285-290.

WEI Ting-Jia, CHE Hui-Ying, HUANG Xi, WENG Jing-Jin, QIN Jiang-Yuan, SU Ji-Ping. A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAA receptors. Acta Physiol Sin 2017; 69 (3): 285-290 (in Chinese with English abstract).