Effects of Roflupram on NOD-like receptor thermal protein domain asso-ciated protein 3,cysteine aspartic acid specific protease-1,interleukin-1 β,and tumor necrosis factor-α in hippocampus of noise-induced tinnitus mice
Objective To investigate the effects of Roflumram on NOD-like receptor thermal protein domain associated protein 3(NLRP3),cysteine aspartic acid specific protease-1(caspase-1),interleukin-1 β(IL-1β),and tumor necrosis factor-α(TNF-α)in hippocampus of noise-induced tinnitus mice.Methods A total of 24 specific pathogen free male C57BU6J mice aged six to eight weeks,weighing 18 to 20 g,were selected and divided into control group,noise exposure group,Roflupram intervention group,and Roflupram toxicity detection group with six mice each by random number table method.Among them,the noise exposure group and the Roflupram intervention group were made by single exposure of 100 dB wide-band white noise for 2 h,the Roflupram intervention group and the Roflupram toxicity detection group were injected with Roflapram[1 mg/(kg·d)]for 7 d,and the noise exposure group and the control group were injected with the same amount of normal saline for 7 d.After the experiment,auditory brainstem response(ABR)and tinnitus behavior were detected in the four groups,and the basement membrane of cochlea in the four groups was fluorescently stained.Real-time fluorescence quantification and western blot were used to detect the mRNA and protein levels of NLRP3,caspase-1,IL-1 β,and TNF-α in the hippocampus of control group,noise exposure group,and Roflupram intervention group.Results After intervention,there was no significant change in ABR response threshold in the four groups compared with before intervention.The gap prepulse inhibition of acoustic startle response inhibition ratio(GPIAS％)in the noise exposure group was lower than that in the control group,and the GPIAS％in the Roflupram intervention group was higher than that in the noise exposure group(P＜0.05).There was no significant difference in GPIAS％between Roflupram toxicity detection group and control group(P＞0.05).Fluorescence staining of the basement membrane of cochlea in the four groups showed no obvious abnormalities in the internal and external hair cells.The mRNA and protein expression levels of NLRP3,caspase-1,IL-1[3,and TNF-α in noise exposure group were higher than those in control group,and those in Roflupram intervention group were lower than those in noise exposure group(P＜0.05).Conclusion A mouse model of tinnitus without significant hearing loss can be successfully established by 100 dB wide-band white noise.Roflupram has no obvious ototoxicity.Tinnitus induced by noise exposure may be related to the expression of inflammatory factors in hippocampus.
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