P38MAPK Is Involved In The Formation Of Endolymphatic Hydrops By Regulating AQP2

Objective: In this experiment,an animal model of endolymphatic hydrops in guinea pigs was prepared by using dd AVP.By detecting two proteins,P-P38 MAPK and AQP2,the effect of P38MAPK-specific inhibitor SB203580 on the degree of endolymphatic hydrops was investigated,and P38 MAPK was discussed.Whether to participate in the formation of endolymphatic hydrops by regulating AQP2.Methods: 45 healthy guinea pigs with a threshold of less than 40 d B SPL and DPOAE passed were randomly divided into three groups: blank control group(9): intraperitoneal injection of normal saline at the same dose as the hydrops group for 10 consecutive days;hydrops Group(18): Intraperitoneal injection of desmopressin acetate 6μg / kg / d for 10 consecutive days;Inhibitor group(18):Intraperitoneal injection of desmopressin acetate 6μg / kg / d,intraperitoneal injection 15 minutes later SB203580 30μg / kg / d for 10 consecutive days.Guinea pigs in all groups were tested for ABR and DPOAE 7 days after the drug was stopped,and samples were taken at the same time.HE staining was used to observe the degree of endolymphatic effusion in each group.Immunohistochemistry and real-time fluorescence quantitative PCR were used to detect the expression of P-P38 MAPK and AQP2 in the cochlea of guinea pigs.Results: 1.Behavioral observation and hearing detection: during the whole experiment,the guinea pigs in each group did not show any symptoms and signs such as slow hearing response,unsteady gait,fear of cold microlight,spontaneous ocular shock,etc.,and there was no significant change in ABR threshold and DPOAE detection before and after administration.2.Morphological observation: the water accumulation in endolymph of guinea pigs in each group was observed by HE staining,and the water accumulation rate in the blank control group was 0%.In the cochlea sections of 12 guinea pigs in the hydrocephalus group,9 patients presented with membranous hydrocephalus(75%),including 1 patient with severe hydrocephalus,2 patients with moderate hydrocephalus,and 6 patients with mild hydrocephalus.Among the 12 cochlear sections of guinea pigs in the inhibitor group,4 of them presented with membranous hydrocephalus(33%),among which 4 had mild hydrocephalus but no moderate or severe hydrocephalus.3.Immunohistochemical: p-P38mapk: p-P38 mapk is expressed in the cochlea of guinea pigs in each group,and is widely expressed in vascular veins(St V),spiral ligament(SPL),vestibular membrane(RM),Corti,s organ(OC),spiral margin(SLM)and spiral ganglion(SG).Compared with other parts,the expression of spiral ganglion was weaker in each group(p<0.01).There was no significant difference in residual expression.Compared with the blank control group,p-P38 mapk expression in the same site was significantly enhanced in both the hydrus group and the inhibitor group,and the expression in the hydrus group was higher than that in the inhibitor group,with statistically significant differences(P <0.01).AQP2: AQP2 is expressed in the cochlea of guinea pigs in each group,and is widely expressed in vascular veins(St V),spiral ligament(SPL),vestibular membrane(RM),Corti,s organ(OC),spiral margin(SLM)and spiral ganglion(SG).At the helical ganglion,there was no significant difference in AQP2 expression between the groups(p=0.365).With the exception of spiral ganglion,the expression of AQP2 in guinea pig cochlea in both the hydrus group and the inhibitor group was significantly higher than that in the blank control group,and the expression in the hydrus group was higher than that in the inhibitor group,with statistically significant differences(p<0.01).4.Real-time quantitative PCR results: P38 mapk m RNA expression in guinea pig cochlea was significantly enhanced in both the hydrops group and the inhibitor group,compared with the blank control group.Compared with the inhibitor group,the expression level of the hydrops group was higher than that of the inhibitor group,and the differences were statistically significant(p<0.01).AQP2: compared with the blank control group,the m RNA expression levels of AQP2 in guinea pig cochlea were significantly enhanced in both the hydronephrosis group and the inhibitor group.Compared with the inhibitor group,the expression level of the hydrops group was higher than that of the inhibitor group,and the differences were statistically significant(p<0.01).Conclusion: 1.Systemic application of desmopressin acetate can induce the formation of Endolymphatic hydrops.2.Endolymphatic hydrops is mainly caused by AQP2 induction in vascular veins,spiral ligaments,vestibular membrane,Corti,s organ,spiral margin,etc.and the spiral ganglion may not participate in the Endolymphatic hydrops.3.P38 MAPK is involved in the formation of Endolymphatic hydrops by regulating AQP2;P38MAPK inhibitor can reduce the degree of Endolymphatic hydrops.