长期注射水杨酸钠大鼠ABR及下丘谷氨酸脱羧酶-67表达的变化  

Effects of Long Term Injection of Sodium Salicylate on the ABR and Expression of GAD67 in Rat Inferior Colliculus

作　　者：吴莎[1] 华清泉[1] 杨琨[1] 肖伯奎[1] 张志敏[1] 

机构地区：[1]武汉大学人民医院耳鼻咽喉一头颈外科,武汉430060

出　　处：《听力学及言语疾病杂志》2014年第2期148-151,共4页Journal of Audiology and Speech Pathology

基　　金：国家自然科学基金青年基金(81100712)资助

摘　　要：目的观察长期注射水杨酸钠对大鼠听性脑干反应(ABR)及下丘谷氨酸脱羧酶-67(GAD67)表达的影响。方法将18只成年健康Wistar大鼠随机分为水杨酸钠组、生理盐水组、对照组,每组6只。水杨酸钠组肌肉注射10%水杨酸钠175mg/kg,2次/天,连续28天;生理盐水组每天相同时间注射等量生理盐水;对照组不注射任何药物。造模结束后,使用美国TDT系统对三组大鼠进行ABR反应阈及波Ⅲ潜伏期检测,然后将大鼠断头处死并取脑,剥离下丘。采用蛋白质印迹(Western blot)方法检测下丘GAD67蛋白表达的变化。结果①水杨酸钠组、生理盐水组、对照组ABR反应阈分别为61.67±4.08、33.33±2.58、35.83±2.04dB SPL,波Ⅲ潜伏期分别为3.97±0.28、3.51±0.11、3.52±0.09ms。水杨酸钠组较生理盐水组、对照组ABR反应阈明显升高,波Ⅲ潜伏期明显延长(P<0.01),而生理盐水组与对照组差异无统计学意义(P>0.05);②水杨酸钠组下丘GAD67蛋白表达水平明显高于生理盐水组、对照组(P<0.01),而生理盐水组与对照组下丘GAD67蛋白表达水平差异无统计学意义(P>0.05)。结论长期注射水杨酸钠可导致大鼠下丘GAD67蛋白表达水平升高,GAD67蛋白表达的上调可能作为一种负反馈以代偿去抑制所引起的兴奋与抑制的失衡状态,促进抑制性效应的产生,该蛋白表达的改变极有可能作为机体对水杨酸钠耳毒性的抑制性代偿反应和调节机制之一。Objective To observe the effects of long term injection sodium salicylate on the auditory brain- stem response（ABR）and expression of glutamic acid decarboxylase-67 （GAD67） in rat inferior colliculus. Methods Eighteen healthy Wistar rats were randomly divided into three groups：the sodium salicylate group （intramuscular injection of 10% sodium salicylate, 175 mg/kg, twice dally for 28 days）, the saline group （intramuscular injection with saline on same does at the same time） ,the control group （without any treatment）. The rats received ABR after modeling, then were decapitated and inferior colliculus tissues were stripped. Western blot was used to study the dif- ferent expression of GAD67 protein levels in the three groups. Results Compared with the saline group and control group, ABR thresholds of the sodium salicylate group were significantly elevated and latency of wave Ⅲwas aslo sig- nificantly prolonged（P〈0.01）,while there was no significant difference between the saline group and the control group（P〉0.05）. The inferior colliculus GAD67 protein expression level of sodium salicylate group was significantly higher than the saline group and control group（P〈0.01）, while there was no significant difference between the salinegroup and the control group（P〉0.05）. Conclusion Long term injection of sodium salicylate can cause a change in the inferior colliculus of GAD67 protein expression and the up regulation of GAD67 expression may occur as a com- pensatory response to increase inhibiting effect. The change of GAD67 protein expression is likely as a compensatory and regulatory mechanisms for sodium salicylate ototoxicity.

关 键 词：水杨酸钠 听性脑干反应 谷氨酸脱羧酶-67 下丘 

分 类 号：R764.5[医药卫生—耳鼻咽喉科]