Effect Of Cx43 Expression In Cochlea Of Presbycusis Mice On Banded Synaptic Aging

Objective:To study the expression of Cx4 3 in the cochlea of presbycusis mice and its mechanism in the occurrence and development of presbycusis,so as to provide a theoretical basis for the prevention of presbycusis.Methods:C57BL/6J mice were selected for experimental study.They were divided into three groups:old age group,D-gal group and control group.16 month old C57BL/6J mice were selected as the old age group.The D-gal simulated old-age deafness model group was made by the classical D-gal aging model,and the control group was injected with equal volume of normal saline subcutaneously at the back of neck every day.The auditory brainstem potential was measured after pentobarbital sodium combined with cilazine hydrochloride anesthesia.The changes of banded synapses were observed by scanning electron microscope.The expression of Cx43 protein in cochlea was measured by immunoblotting and enzyme-linked immunosorbent assay.The measurement data were analyzed by t-test and one-way ANOVA.The correlation analysis of cochlear Cx43 protein expression,cochlear ribbon synaptic density and ABR threshold was analyzed by Pearson correlation analysis.Results:(1)ABR threshold measurement results:the ABR threshold of the elderly group and D-gal group was significantly higher than that of the normal group(P<0.05),but there was no significant difference between the elderly group and D-gal group(P>0.05).(2)Electron microscopic results of cochlear ribbon synapses:the width of cochlear ribbon synapses in the elderly group and D-gal group was significantly smaller than that in the normal group(P<0.05).(3)Cx43 protein expression:WB results showed that Cx43 protein in the elderly group and D-gal group was significantly lower than that in the normal group(P<0.05),but there was no significant difference between the elderly group and D-gal group(P>.05);ELISA results showed that Cx43 protein in the elderly group and D-gal group was significantly lower than that in the normal group(P<0.05),but there was no significant difference between the elderly group and D-gal group(P<0.05).(4)Cx43 protein expression and auditory brainstem potential ABR:there was a negative correlation between Cx43 protein expression and auditory brainstem potential ABK threshold in three groups of mice(r=0.74,P<0.001).(5)Correlation analysis between Cx43 protein expression and cochlear ribbon synaptic width:there was a positive correlation between Cx43 protein expression and cochlear ribbon synaptic width in three groups of mice(r=0.83,P<0.001).Conclusion:(1)The width of cochlear ribbon synapses decreased in elderly mice and D-gal senile deafness model mice,suggesting that cochlear ribbon synaptic aging may be the key pathological mechanism of senile deafness.(2)The expression of Cx43 protein decreased in the cochlea of aged mice and D-gal senile deafness model mice,and it was positively correlated with the width of cochlear ribbon synapse and negatively correlated with the ABR threshold of auditory brainstem potential,suggesting that Cx43 protein may participate in the occurrence and development of presbycusis by mediating the aging of cochlear ribbon synapse.