| Research background With the development of the economy in western my country,the number of people entering the Qinghai-Tibet High altitude for work,study,tourism,etc.is increasing.However,when people enter the high altitude area from the plain area or enter the higher altitude area from the high altitude area,the high altitude hypoxia will have a certain impact on the body’s blood system,respiratory system,circulatory system,and urinary system.Our previous work found that on the 30th day after the rat moved to the high altitude,the rat’s hearing loss was the most serious,the auditory nerve myelination was reduced,and the structure was incomplete.As the rat was exposed to the high altitude hypoxic environment,the hearing of some rats gradually recovered,that is,the rat’s hearing has undergone the process of acoustic adaptation and then repaired,rats whose hearing fails to recover with prolonged exposure to high altitude hypoxic environment develop hearing loss or even deafness.The impact of hypoxic environment in high-altitude rats can cause damage to the myelin sheath of the auditory nerve.Schwann cells are a kind of astrocytes and are the main cells that form the myelin sheath of the auditory nervous system.Schwann cell myelin formation is regulated by multiple pathways and pathways.It is not clear whether the Hippo signaling pathway is involved in the process of Schwann cell myelin formation after hearing loss under hypoxic environment.The Hippo signaling pathway is involved in the regulation of the proliferation and differentiation of various cells,YAP is the core component of the Hippo pathway,when YAP is transferred to the nucleus,it promotes Schwann cell proliferation,after YAP is knocked out,Schwann cell differentiation is reduced,causing nerves.Myelination is abnormal.It can be seen that the Hippo signaling pathway regulates the regeneration of nerve myelin sheath and the phenotypic transformation of Schwann cells.However,there is no research on the Hippo signaling pathway that regulates the phenotypic conversion of Schwann cells in the auditory nervous system under hypoxic environment to form myelin sheath.Research purposes Using the model of high altitude immigrant rats to understand the impact of high altitude hypoxic environment on the auditory system of migratory rats,and to explore whether the Hippo/YAP signaling pathway is involved in the regulation of hearing damage under hypoxic environment.Methods Eight-week-old Wistar rats were airlifted from Chengdu(500 meters above sea level)to Lhasa,Tibet(3658 meters above sea level),the time when the rats moved to the high altitude was used as the grouping standard,the rats were counted from the first day when the rats reached the high altitude,and on the 30th day they reached the high altitude,for the high altitude group,the same batch of plain rats served as the control group.In the high altitude group and the plain control group,the rats were killed by decapitation and the auditory vesicles were taken,the cochlear tissue was taken out under a dissecting microscope,RNA was extracted,and RNA-seq transcriptome sequencing was performed.Screen the genes related to the Hippo signaling pathway in the high altitude group on the 30th day and the plain control group,and analyze the differential gene expression of the high altitude group and the plain control group on the 30th day.GO and KEGG analysis of functions and pathways in the process of hearing impairment.The results(1)Wistar rats moved from the plain to the high altitude from day 1 to day 30,eating and drinking were normal,activities were normal,and no natural death occurred.With the extension of the time when the rats moved to the high altitude,their body weight increased significantly and their development was normal(P<0.05).(2)GO analysis results of high altitude D30 and plain group:GO analysis of up-regulated differentially expressed genes found that the biological processes that are significantly enriched are: muscle contraction,cardiac muscle contraction,skeletal muscle contraction;the obvious enrichment of Cellular Component are: myofibril,Z disc,proteinaceous extracellular matrix;the obvious enrichment of Molecular Function are:telethonin binding,calcium ion binding,actin filament binding.GO analysis of down-regulated differentially expressed genes found that the biological processes that are significantly enriched are: chemical synaptic transmission,regulation of postsynaptic membrane,regulation of membrane potential;the obvious enrichment of Cellular Component are:integral component of plasma membrane,postsynaptic membrane,neuron projection;the obvious enrichment of Molecular Function are: transmittergated ion channel activity involved in regulation of postsynaptic membrane potential,inhibitory extracellular ligand-gated ion channel activity,GABA-gated chloride ion channel activity.(3)KEGG analysis found that the high altitude group was compared with the plain control group on the 30th day: There are 265 enriched pathways,among which the Hippo signaling pathway is enriched in the process of hearing damage.(4)Hippo signaling pathway and hearing damage related genes:Compared with the high altitude D30 and the plain group,a total of 13 differentially expressed genes in the Hippo signaling pathway were screened.the genes that are up-regulated are: Bmp8a、Ctgf、Wnt1、Wnt10a、Wnt10b、Wnt5a;the genes that are up-regulated are:Bmpr1b、Ccnd1、Crb1、Fzd10、Wnt7a、Wnt7b、Wnt9b.Conclusion(1)The rats migrated from the plain area to the high altitude hypoxic environment without natural death and normal growth and development.(2)The Hippo signaling pathway is involved in the regulation of the hearing loss process of rats in the high altitude group D30 hypoxic environment. |
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