Age-related Changes Of Auditory Function And Expression Of P-ERK1/2?p-ERK5 In Cochlea Of The Senescence Accelerated Mouse, Experimental Research Of HUVEC-C Cultured In Vitro

Objective: To probe age-related changes of auditory function and expression of cochlear phosphorylated extracellular signal-regulated kinase 1/2,phosphorylated extracellular signal-regulated kinase 5 in cochlea of the senescence accelerated mouse and in human umbilical vein endothelial cells(HUVEC-C)under the fuction of inhibitor(BIX02188),for Elucidating the molecular mechanisms of pathogenesis of presbycusis and providing some basic theoretical basis for the treatment of presbycusis.Methods: 3,5,7 months subline rapid aging mice 8(SAMP8)were selected as objects of the study,n = 6,and detected the threshold with 8 kHz tone burst auditory brainstem response,and detected the expression of p-ERK1/2,p-ERK5 in Cochlea by immunohistochemical staining method.At the same time the enlargement of changes associated with aging were analysed.Human umbilical vein endothelial cells were cultred in vitro for 24 hours under the BIX02188(Terminal concentration 2,5,10,15,20?m).The viability and apoptotic rate were detected by MTT colorimetric assay and cell apoptosis assay(Hoechst 33258).The expression of p-ERK5 was detected with Immunofluorescence.Results: Auditory Function:With the increase of age,the threshold of binaural auditory brainstem response of SAMP8 mice increased significantly(P <0.05).The expression of p-ERK1/2,p-ERK5 in cochlear tissue: In different months accelerated mouse cochlea(spiral ganglion cells,inner and outer hair cells and vascular pattern),p-ERK1/2 were expressed.With the increase of age,the optical density significantly reduced(P <0.05).In different months accelerated mouse cochlear tissue(blood vessel pattern),p-ERK5 were also expressed.With the increase of age,the optical density significantly reduced(P <0.05).p-ERK5 was expressed in the nucleus and cytoplasm of HUVEC-C.With BIX02188 concentration increased,the inhibition gradually increased on cells(P <0.05).Percentage of apoptotic cells increased with dose-dependent manner(P <0.05).Positive signal of p-ERK5 was gradually weakened in nucleus of HUVEC-C(P <0.05).Conclusions: With the age-related loss of hearing function,the protein expression level of p-ERK1/2,p-ERK5 decreased in accelerated mouse cochlear tissue.P-ERK1/2,p-ERK5 might be related to maintain the functional status of the cochlea and formed the hearing.BIX02188 couid be suppressed Cell Proliferation of HUVEC-C and effectively blocked the phosphorylation of ERK5.P-ERK5 might be related to the functional status of vascular endothelial cells.So as to provided the basis for the experiment.The experimental foundations could be provided by separating the guinea pig cochlea vascular endothelial cells and establishing the blood labyrinth barrier model.