白细胞介素-18在传导性听觉剥夺致听力损失过程中的作用机制OA

Objective To investigate the mechanism of IL-18 in the process of hearing loss induced by long-term conductive auditory deprivation.Methods C57BL/6J mice at postnatal 12 days were randomly assigned to normal control(Ctrl),long-term conductive auditory deprivation(LTD)and long-term conductive auditory deprivation removal(LTR)groups.The LTD group underwent 6 weeks of bilateral auditory deprivation,while the LTR group received deprivation removal after 6 weeks of bilateral auditory deprivation with continued observation for 8 weeks.Auditory function was assessed using auditory brainstem responses(ABRs).Transcriptome sequencing was performed on the cochlear in successfully modeled mice and controls.Immunofluorescence staining was used for hair cells and ribbon synapses assessment,as well as detection of IL-18 expression in the inner ear.Western blot was used for detection of IL-18 expression levels in the entire cochlea.Results ABR thresholds were significantly elevated in the LTD group with no significant recovery even 8 weeks after deprivation removal.Immunofluorescence staining revealed significant reduction in the number of ribbon synapses after deprivation removal.RNA sequencing(RNA seq)indicated significant enrichment of immune and inflammation-related biological processes in the cochlea following auditory deprivation removal.Immunofluorescence staining revealed significantly elevated IL-18 expression in cochlear basilar membrane region in the LTR group compared to the control.Western blot revealed elevated expression levels of IL-18 in the cochlea in the LTR group.Conclusions Long-term conductive auditory deprivation induces irreversible hearing loss in mice,with damage to the cochlear ribbon synapses serving as the primary pathological mechanism.The high inflammatory state in the inner ear induced by conductive auditory deprivation,particularly marked elevation of IL-18 levels in the cochlear basilar membrane,may be a key factor contributing to this damage.