中文摘要：

目的本研究采用对大鼠急性及慢性水杨酸盐腹腔注射建立耳鸣动物模型,通过检测大鼠耳蜗核中肿瘤坏死因子α（TNF-α）,白介素-1β（IL-1β）,白介素6（IL-6）以及NMDA受体亚基（NR2B）m RNA及其蛋白的表达,了解慢性水杨酸盐诱导的耳鸣动物耳蜗核中是否出现炎症因子表达的改变,以探讨炎症因子在耳鸣中的作用。方法实验动物随机分为4组,按给药时间分别为：正常对照组、急性注射2小时组、慢性注射14天组、停药后恢复14天组。各组大鼠断头处死后迅速分离出耳蜗核;采用SYBR Green实时荧光定量PCR（real-time reverse transcriptase polymerase chain reaction,real-time RT-PCR）及Western blot（蛋白质印迹）方法,检测各组大鼠耳蜗核TNF-α,IL-1β,IL-6及NR2B基因m RNA及其蛋白的表达,观察各组间的差异。结果（1）在慢性注射14天组,TNF-α和NR2B m RNA及其蛋白表达水平较正常对照组、急性注射2小时组、停药后恢复14天组高,且差异有统计学意义（p〈0.05）;急性注射2小时组、慢性注射14天组、停药后恢复14天组IL-1βm RNA水平较正常组高,慢性注射14天组、停药后恢复14天组IL-1β蛋白水平较正常组高,差异有统计学意义（p〈0.05）;IL-6 m RNA及其蛋白表达水平在四组之间无明显差异;（2）TNF-α和NR2B m RNA表达具有明显的正相关（p〈0.01）;IL-1β和NR2B m RNA表达无明显正相关（p〉0.05）。结论（1）长期注射水杨酸盐可能通过上调耳蜗核中TNF-α,IL-1β和NR2B基因表达导致大鼠耳鸣;（2）TNF-α和NR2B可能在水杨酸盐诱发耳鸣的过程中起协同作用。

英文摘要：

Objective Salicylate has the potential to cause reversible tinnitus. However, few reports have examined the as- sociation between tinnitus and inflammatory cytokines in the cochlear nucleus in a rat model of tinnitus. To investigate the central mechanisms in tinnitus induced by salieylate, we examined the expression levels of tumor necrosis factor-α （TNF-α）, interleu- kin-1β （IL-1β）, interleukin-6 （IL-6）, N-methyl D-aspartate receptor subunit 2B （NR2B） genes in the cochlear nucleus of rats following salicylate administration. Methods Rats were divided into four groups： control group; acute treatment group with saliey- late injected once; chronic treatment groups with repetitive injections of salicylate for 14 days; recovery groups with 14 days, post-chronic salicylate administration, and then we investigated the expression levels of TNF-α, IL-6, and NR2B mRNA and protein in the cochlear nucleus. Results The mRNA and protein expression levels of TNF-α and NR2B were up-regulated in chronic treatment groups（p〈0.05）. These levels returned to baseline 14 days after cessation of treatment. Compared to control group, IL-1β mRNA expression was up-regulated in the acute group, chronic group and recovery group （p〈0.05）, and the protein expression levels of IL-1β increased in the chronic group and recovery group （p〈0.05）. However, IL-6 gene expression was not significantly different in any of the groups. In addition, expression levels of the TNF-α mRNA were positively correlated with those of the NR2B mRNA in cochlear nucleus（p〈0.01）. Conclusion These data revealed that chronic salicylate administration markedly, but reversibly, induces tinnitus, augments the expression of TNF-α, IL-1β and NR2B in the cochlear nucleus; Altera- tions of TNF-α might lead to tinnitus directly or via modulating the NMDA receptor.