Effects of Salicylate on Inflammatory Cytokines Expression in Cochlear Nucleus in Rats

HU Shousen; MEI Ling; CHEN Jianyong; LV Jingrong; HUANG Zhiwu; WU Hao

doi:10.3969/j.issn.1672-2922.2015.01.026

Abstract：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 salicylate, 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 salicy?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-αand 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-1βmRNA expression was up-regulated in the acute group, chronic group and recovery group (p<0.05), and the protein expression levels of IL-1βincreased 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-a 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-1βand NR2B in the cochlear nucleus;Altera?tions of TNF-αmight lead to tinnitus directly or via modulating the NMDA receptor.