耳蜗局部应用NR2B受体阻滞剂对水杨酸钠致豚鼠螺旋神经节细胞损伤的拮抗作用

Blocking NR2B Receptor Reversed the Process of Cytotoxicity to Spiral Ganglion Neurons Induced by Sodium Salicylate in Guinea Pig

刘渊;尹时华;黄训健;周琦;舒竞铖;韦顺莲;

1:广西医科大学第一附属医院耳鼻咽喉头颈外科

摘要
目的通过圆窗龛局部给予特异性NR2B受体阻滞剂艾芬地尔,探讨其拮抗水杨酸钠致豚鼠螺旋神经节细胞损伤的作用。方法将ABR阈值小于40dB SPL的健康花色豚鼠48只随机分为4组,每组12只,Ⅰ组为空白对照组;Ⅱ组为人工外淋巴液(artificial perilymph,APL)组,左耳圆窗龛注人APL 60μl;Ⅲ组为水杨酸钠组,左耳圆窗龛注入APL 60μl,腹腔注射水杨酸钠;IV组为艾芬地尔组,左耳圆窗龛注入溶于APL的艾芬地尔(10μmol/L)60μl后,腹腔注射水杨酸钠。水杨酸钠注射量为400mg·kg-1·d-1,连续注射7天。停药并行ABR测试后将动物处死,取出左侧耳蜗,每组随机取6只动物进行免疫组织化学染色观察耳蜗螺旋神经节(SGN)caspase-3表达情况,6只行原位末端转移酶标记技术(terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end labeling assay,TUNEL)法检测螺旋神经节细胞凋亡率。结果给药后,I、II、III、IV组动物左耳ABR反应阈分别为31.67±5.16、33.33±5.17、64.17±7.36、49.17±5.85dB SPL;免疫组织化学染色显示,Ⅰ、Ⅱ组螺旋神经节细胞中caspase-3的表达量差异无统计学意义,Ⅲ、IV组螺旋神经节细胞中caspase-3的表达量较Ⅰ、Ⅱ组显著增高(P<0.01),IV组螺旋神经节细胞中caspase-3的表达量较Ⅲ组明显降低(P<0.01)。TUNEL法检测结果示,Ⅰ、Ⅱ组SGN细胞凋亡率无显著差异,Ⅲ、IV组SGN细胞凋亡率较Ⅰ、Ⅱ组显著增高(P<0.01),IV组SGN细胞凋亡率较Ⅲ组明显降低(P<0.01)。结论耳蜗局部特异性阻断NR2B受体可以拮抗水杨酸钠致豚鼠螺旋神经节细胞的损伤。
关键词
艾芬地尔;水杨酸钠;耳蜗;圆窗膜;螺旋神经节
基金项目(Foundation):
国家自然科学基金(30860312);; 广西自然科学基金(桂科自0728134);; 国家博士后科学基金(20080440819)联合资助
作者
刘渊;尹时华;黄训健;周琦;舒竞铖;韦顺莲;
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