耳鸣大鼠NMDA受体亚型1、2A、2B的表达研究

目的研究耳鸣大鼠听皮层NMDA（N-甲基-D-天冬氨酸,N-methyl-D-aspartate）受体亚型1、2A、2B（NR1、NR2A、NR2B）的表达变化,从而推测其在耳鸣的发生中可能的作用机制。方法按照随机化原则将动物分成3组,每组9只：A组为耳鸣模型组、B组为生理盐水组、C组为空白对照组。A组通过腹腔注射水杨酸钠并用食物抑制法进行验证。造模成功后运用核酸荧光染料SYBR Green实时荧光定量PCR（Polymerase Chain Reaction,聚合酶链反应）方法检测NMDA受体三种亚型的表达情况。结果NR1在A组的表达显著低于C组（P〈0.05）,NR2A在A组的表达则显著高于C组（P〈0.05）,而A、C两组之间NR2B的表达差异比较无统计学意义（P〉0.05）。NMDA受体三种亚型B、C两组之间表达差异比较均无统计学意义（P〉0.05）。A组NR2A、NR2B与NR1表达量的比值较C组均增大。结论耳鸣大鼠听皮层NMDA受体调节亚基的调控作用增大,突触局部受体蛋白质合成改变,听皮层发生了与NMDA受体相关的可塑性变化,这可能是耳鸣产生的机制之一。

Expression of NMDA receptor subtypes 1, 2A and 2B in a rat model of tinnitus

Objective To study expression of N-methyl-D-aspartate (NMDA) receptor subtypes 1 (NR1), 2A (NR2A) and 2B (NR2B) in the auditory cortex in a rat model of tinnitus for their potential roles in tinnitus pathogenesis. Methods Twenty seven rats were randomly divided into three groups (n=9) to receive salicylate as tinnitus models (Group A), to be treated with normal saline (Group B) or to serve as non-treatment controls (Group C). Tinnitus modeling was verified through feeding inhibition following intra-peritoneal administration of salicylate. Expression of the three NMDA receptor subtypes was examined by real-time SYBR Green PCR assays. Results NR1 expression in Group A was lower than Group C (p<0.05), while NR2A expression was higher than Group C (p < 0.05). NR2B expression showed no statistically significant difference between Groups A and C. No statistically significant differences were noticed between Groups B and C for either subtype. The rate of expression for all three receptor subtypes was higher in Group A than Group C. Conclusion The data seem to suggest increased regulatory functions by NMDA receptor subtypes in the auditory cortex in rats with tinnitus, which is likely a result of change in protein synthesis in local synapses. This may indicate an NMDA receptor-dependent plastic change in the auditory cortex, which may be a mechanism for tinnitus.