TLR4阻滞剂降低耳蜗炎症改善噪声性耳聋的研究OA

Objective To demonstrate suppression of can noise-induced cochlear inflammation by TLR4 blocker in protecting hearing function.Methods SD rats were randomly divided into a normal control group,a noise exposure group,a noise explore with intratympanic TAK242(a TLR4 inhibitor)injection group,and a noise explore with intratympanic DMSO injection group.Auditory brainstem response(ABR)data were collected on the 3rd and 14th days post noise exposure.On the 3rd day post noise exposure,the cochlea was harvested to measure TLR4,myeloid differentiation factor 88(MyD88),IL-1β and TNF-αby western blot and immunohistochemistry,and to measure NF-κB p65 activity with immunofluorescence staining.TUNEL assay was used to display apoptotic cells.Results After noise explore,the expression of TLR4,MyD88,NF-κB and TNF-α was significantly elevated in the spiral ligament,spiral ganglion neuron and Deiters'cells.In stria vascularis,the expression of TLR4,NF-κB and TNF-α was consistently increased,while MyD88 showed no significant change.TAK242 treated rats showed significantly lower expression of MyD88,IL-1βand TNF-α,lower activity of NF-κB,and fewer apoptotic cells in spiral limbus,compared to untreated rats,as well as better ABR responses.Conclusions TLR4 inhibitors can suppress noise induced inflammation in the spiral ligament,stria vascularis,spiral ganglion and organ of Corti,thus protecting hearing function.