巨噬细胞诱导的炎症反应在噪声导致的隐匿性听力损失中的作用及机制OACHSSCD

Objective To clarify the relationship and possible mechanisms between macrophages and noise-induced hidden hearing loss.Methods A mouse model for cochlear macrophage depletion was constructed by injecting liposomal clodronate Clophosome-A(LCCA)through the round window.Using previously constructed mouse model of noise-induced hidden hearing loss,mice were divided into four groups:control group(CON group),LCCA injection group(LCCA group),noise exposure group(NE group),and noise exposure with LCCA injection group(NE+LCCA group).Auditory brainstem response(ABR)measurements were conducted to assess changes in auditory function by analyzing the auditory thresholds at different frequencies,click-evoked auditory thresholds,ABR Ⅰ wave amplitudes and latencies induced by 80 dB SPL click stimulation.Additionally,morphological changes in ribbon synapses in the cochlear basilar membrane were observed through staining after sectioning.Finally,the mRNA expression levels of pro-inflammatory factors were measured using quantitative PCR.Results Compared with CON group,the auditory thresholds of NE group significantly increased(P＜0.000 1),ABR Ⅰ wave amplitudes induced by 80 dB SPL click significantly decreased(P＜0.000 1),the latencies significantly prolonged(P＜0.000 1),and the number of ribbon synapses was significantly decreased(P＜0.000 1),while the expression levels of pro-inflammatory factors were significantly increased(P＜0.000 1).The above indicators in NE+LCCA group showed significant improvement compared with NE group(P＜0.05),but still fell short of the normal levels(P＜0.05).Using LCCA alone did not affect auditory function,number of ribbon synapses,or expression of pro-inflammatory factors.Conclusion Macrophages play a role in the progression of noise-induced hidden hearing loss by intensifying the inflammation,resulting in structural and functional damage to the inner ear.