Role Of Glucose Metabolism Imaging By PET/CT In The Early Warning Of Aging Of Auditory Cortex In Guinea Pigs With Age-Related Hearing Loss

Objective:To investigate the time sequence and correlation of changes in auditory function and glucose metabolism in auditory cortex of age-related hearing loss guinea pigs,the role of PINK1/Parkin mediated mitophagy,and PET/CT in the early warning of the aging process of auditory cortex of guinea pigs.Methods:1.Grouping and modeling.56 adult guinea pigs were randomly divided into two groups,including the control group（CG,n=8）and D-galactose model group（DG,n=48）.Moreover,the 18-month guinea pigs were in the elderly group（EG,n=8）.Guinea pigs were injected subcutaneously with 300mg/kg/day D-galactose in DG.According to the different duration of continuous injection of D-galactose,they were divided into 6 groups of 7,14,21,28,35 and 42 days（n=8 for each group）.The guinea pigs were fed with conventional feed without treatment in the CG and EG.2.Audiological test.After the model was established,the ABR thresholds were detected in all groups.3.Glucose metabolism detection by PET/CT.The average ratio of the maximum standard uptake values（SUVmax）were obtained between the auditory cortex and cerebellum in each group by PET/CT.4.Correlation analysis was performed between auditory function and glucose metabolism in auditory cortex.5.Protein detection by western blot.The expression levels of PINK1,Parkin and Beclin1 protein were measured in the auditory cortex of each group by western blot,and GAPDH was used as the internal reference protein.6.Statistical method.All data were expressed as mean±standard deviation（x±s）.The differences among the groups are compared by one-way ANOVA.The difference is considered to be statistically significant as P<0.05.Additionally,LSD method was applied when the variance is homogeneous,and Tamhane’s T2 method was applied when the variance is uneven for inter group comparison.Pearson correlation analysis was used for correlation analysis.Results:1.ABR threshold.There were significant differences in ABR threshold among CG,DG,and EG（F=160.13,P=0.000）.Compared with the CG,the ABR threshold increased significantly in DG（7,14,21,28,35 and 42-day groups）and EG（P<0.05）.In addition,compared with the EG,the ABR threshold decreased significantly in DG（7,14,21,28 and 35-day groups）（P<0.05）,and had no significant change in 42-day group（P>0.05）.2.Changes of glucose metabolism in auditory cortex by PET/CT.There were significant differences in the average ratio of SUVmax between auditory cortex and cerebellum among CG,DG,and EG（F=41.54,P=0.000）.Compared with the CG,the average ratio of SUVmax between auditory cortex and cerebellum in DG（14,21,28,35 and 42-day groups）and EG decreased（P<0.05）.Furthermore,there were increases in the average ratio of 7,14,21 and28-day groups（P<0.05）,and no significant changes in 35 and 42-day group（P>0.05,compared with the EG）.3.Correlation between auditory function and glucose metabolism.There was a significant negative correlation between auditory function and glucose metabolism（r=-0.913,P=0.000）.4.Changes of PINK1,Parkin and Beclin1 protein expression in auditory cortex.There was significant difference in the expression of PINK1,Parkin and Beclin1 protein in auditory cortex among CG,DG and EG(F_pink1=106.15,F_parkin=190.02,F_Beclin1=93.44,P=0.000).Compared with CG,the protein levels of PINK1,Parkin and Beclin1 increased in the auditory cortex of DG（7,14,21,28,35 and42-day groups）and EG（P<0.05）.Moreover,compared with EG,the expression of PINK1,Parkin and Beclin1 protein decreased in the auditory cortex of 7,14,21,28 and 35-day groups（P<0.05）,had no significant difference in 42-day group（P>0.05）.Conclusion:1.The hearing function and glucose metabolism function of auditory cortex decreased gradually in guinea pigs during the occurrence and development of age-related hearing loss.2.There were significant correlations in the time sequence between hearing loss and glucose metabolism in auditory cortex of guinea pigs with age-related hearing loss.3.The mitophagy mediated by PINK1/Parkin may promote the early remodeling process of auditory cortex in guinea pigs with age-related hearing loss.4.PET/CT may be an early warning method for hearing loss and aging of auditory cortex in guinea pigs with age-related hearing loss.