Study On Glucocorticoid Therapy After Acute Hearing Loss And Acceptable Noise Level Tests

Objective:In this study,we aimed to investigate the role of MAP Kinase Phosphatase-1(MKP-1)in glucocorticoid resistance and that of rosiglitazone(RSG)in restoring glucocorticoid sensitivity in a guinea pig model of lipopolysaccharide(LPS)-induced sudden sensorineural hearing loss(SSHL).At the same time,we studied whether rosiglitazone could improve the hormone resistance of the model by promoting MKP-1 expression.We also studied the acceptable noise level(ANL)test before hearing aids were selected in the case of ineffective drug treatment after hearing loss.The influence of different methods on acceptable noise level test is discussed,and the reliability of acceptable noise level test is improved.Method:Guinea pigs were divided into five groups.Before treatment,closed sound field ABR test was performed to evaluate hearing.Treatment: artificial perilymph group,LPS group,LPS + dexamethasone group,LPS + rosiglitazone group,LPS + dexamethasone + rosiglitazone group.ABR thresholds were tested before surgery and 48 h after surgery in all subjects.Immunofluorescence technique was used to evaluate the localization of MKP-1.Western Blot assessed the content of MKP-1 in the cochlea,and the morphology of the cochlea was evaluated by HE staining of paraffin sections;20 healthy subjects(10 males and 10 females)participated in four different methods of ANL tests: ANL was tested with Mandarin speech materials using a loudspeaker or earphones,with each subject tested by himself or by the audiologist.The presentation and response modes were as follows:(1)loudspeaker with self-adjusted noise levels using audiometer controls(LS method);(2)loudspeaker with the subject signaling the audiologist to adjust speech and noise levels(LA method);(3)earphones with self-adjusted noise levels using audiometer controls(ES method);and(4)earphones with the subject signaling the audiologist to adjust speech and noise levels(EA method).Four groups of data were analyzed by Two-way repeated measures analyses of variance(ANOVA),and the differences between the four groups were compared.At the same time,the correlation of the four groups of data was analyzed.Evaluate the impact of different methods on ANL test.Result:LPS group had severe hearing loss,while LPS + dexamethasone + rosiglitazone group had the best protective effect on hearing loss.Immunofluorescence showed that MKP-1 was mainly located in the cytoplasm and a few in the nucleus.Morphological observation showed that the spiral ganglion was most severely damaged in LPS group,and the ratio of nucleus to plasma decreased.Some spiral ligaments were sparse and disordered,and the distance between them and the lateral wall of the cochlea was widened.There was no significant difference in ANL obtained by four methods.There was no significant correlation between MCL and ANL,the BNL and ANL in the same method.The correlation among ANL,MCL and BNL obtained from any two methods is significant.Conclusion:The inability of glucocorticoid to effectively up-regulate MKP-1 may be one of the reasons for glucocorticoid resistance after acute hearing loss.Rosiglitazone can improve the protective effect of acute inflammatory glucocorticoid therapy in the inner ear;and the results of ANL obtained by four methods are comparable and reliable.In clinic,after the drug treatment of hearing loss is ineffective,audiologists can select appropriate ANL test methods to evaluate the hearing aids of patients according to the equipment and the situation of the subjects.