地塞米松通过抑制内耳炎症干预噪声性聋的机制研究OA

Objective To investigate whether dexamethasone has a protective effect against noise-induced hearing loss and its molecular pathological mechanisms.Methods Five-week-old male C57BL/6J mice were exposed to 100 dB SPL white noise for 2 hours,followed by a second noise exposure(NE)under the same conditions 14 days after the 1st NE to establish a mice model of noise-induced hearing loss.Prior to the 1st NE,dexamethasone was administered via intraperitoneal injection for 7 consecutive days.The effects of dexamethasone on noise-induced hearing loss were evaluated using auditory brainstem response(ABR)audiometry,immunofluorescence staining,ELISA,and Q-PCR.Results The number of ribbon synapses in the cochlea after NE significantly decreased(P<0.01),with a gradual increase of the level of inflammatory cytokine IL-18 in the inner ear(P<0.01).ELISA and Q-PCR analyses demonstrated downregulated expression of inner ear inflammatory cytokine IL-18 after NE with intraperitoneal injection of dexamethasone(P<0.01).Immunofluorescence staining showed significantly higher number of ribbon synapses with dexamethasone treatment than with saline intervention after NE,particularly after the 2nd NE(P<0.05).ABRs indicated significantly better thresholds with dexamethasone treatment at 1 day(4,16 and 24 kHz)and 7 days(4 and 16 kHz)after the 1st NE(P<0.05),and at 1 day(4 and 24 kHz),7 days(4,8 and 24 kHz),and 14 days(4,8 and 16 kHz)after the 2nd NE(P<0.05).Conclusions Dexamethasone can protect cochlear ribbon synapses against NE through inhibition of inner ear inflammation,providing a new insight into therapeutic strategy for noise-induced hearing loss.