Research On The Regulation Mechanism Of PI3K/AKT Signaling Pathway In Auditory Acclimatization At High Altitude Environment

Research background Areas with an altitude of more than 2500 meters are called plateau areas.The plateau is characterized by low pressure and low oxygen.Some scholars have found that the special environment of the plateau has a certain degree of damage to the human auditory system.Under the continuous stimulation of the hypoxic environment,the auditory system will undergo compensatory adaptation to reduce the hearing damage(sound acclimatization).Myelin sheath is a layer of electrical insulation wrapped around the nerve axon.It is the basis for maintaining the normal function of the nervous system and the structural basis for maintaining the transmission of nerve signals along the axon at a faster speed.The repair of auditory nerve myelin sheath is related to Sehwann cells(SCs).SCs are the main structural and functional cells of peripheral nerve tissue and the core of the peripheral nervous system.They play a functional role in the process of peripheral nerve injury,regeneration and repair.In the process of myelination,there are some signaling pathways involved,among them,the phosphatidylinositol 3-kinase(PI3K)/ Serine-threonine kinase(AKT)signaling pathway is used to regulate hearing learning.And it's one of the main signal transduction pathways in the formation of myelin during the process.PI3 K can phosphorylate PIP2 to PIP3.PIP2 and PIP3 act on the PI3 K / AKT signaling pathway,both of which are important intracellular The second messenger plays an important role in cell proliferation and metabolism.Among them,AKT is a serine / threonine kinase composed of about 480 amino acid residues.It is an important target protein downstream of the PI3 K signaling pathway and can regulate various basic activities such as cell growth,proliferation,and survival.The mammalian target of rapamycin(m TOR)is an important target downstream of PI3 K / AKT signaling pathway.m TORC1 is the gatekeeper for various anabolic reactions,including m RNA translation and biosynthesis of lipids,purines,and pyrimidines.P70 ribosomal S6 protein kinase(p70S6K)is a direct target of downstream of m TOR.P70S6 K can affect the axon growth by affecting the expression of amino acids or by increasing the synergy between actin and cytoskeleton Regulate nerve cell orientation.Phosphatase and tensin homolog deleted PTEN(phosphatase and tensin homolog deleted on chromosome ten)is the upstream inhibitor of PI3 K / AKT signaling pathway,which can dephosphorylate PIP3 to PIP2 and lose its activation.The tuberculous sclerosis complex(TSC)complex consists of TSC1,TSC2,and TBC1D7 subunits.TSC1 and TSC2 are important inhibitors upstream of m TOR.Research purpose This study uses epidemiological investigation to understand the hearing of Han college students.Through the establishment of animal models to study the impact of plateau migration time on the auditory system,explore the causes of plateau hypoxia auditory acclimation,and clarify the expression of the relevant factors regulating the PI3 K / AKT signaling pathway in the process of hearing acclimation in a hypoxic environment.Poor service and the treatment of peripheral myelin sheath disease provide a theoretical basis.Methods The research in this subject used a combination of epidemiological investigation and animal models.Epidemiological survey: In September 2019,a random sampling method was used to conduct a questionnaire survey and pure-tone listening test for 17-25 year-old Han college students at Tibet University.Animal model: randomly selected 54 wistar rats(male rats)living in the plain area,2 months old,weighing 200g-300 g.The plain wistar rats as the control group and the index changes of the plateau on the 15 days,30 days,60 days,120 days,and 180 days are used as the experimental group.HE staining was used to observe the morphological changes of rat cochlea;RT-PCR method was used to detect the m RNA levels of PI3 K / AKT signaling pathway PI3 K,AKT,m TORC1,p70S6 K,TSC1,TSC2 and PTEN in the cochlear tissue of each group of rats.Results Epidemiological survey: survey 126 people,the prevalence of hearing loss is 4.76%;the prevalence of right ear(4.76%)is higher than the prevalence of left ear(2.38%)(p<0.05);male prevalence The rate(6.78%)was not statistically different from the female prevalence rate(2.99%)(P>0.05);overall,with the increase of grade and age,the prevalence of hearing loss decreased(p<0.05),respectively: 7.84 %,4.35%,0%,0%,0%.Animal model: HE staining showed that: within 60 days,the rat cochlea had different degrees of damage.From February to June,the degree of cochlear damage gradually reduced.RT-PCR results showed that compared with the plain control group,the PI3 K m RNA level of the cochlear tissue of the Wistar rat in the experimental group was reduced in 1-60 days(P>0.05),and60-180 days the PI3 K m RNA level of the Wistar rat in the experimental group was increased(P>0.05);1-60 days,the m RNA levels of AKT,m TORC1,p70S6 K in cochlear tissue of Wistar rats in experimental group decreased(P<0.05),the m RNA levels of PTEN,TSC1,TSC2 increased(P<0.05),60-180 days,Wistar rats in the experimental group had higher AKT,m TORC1,and p70S6 K m RNA levels(P <0.05),while PTEN,TSC1,and TSC2 m RNA levels decreased(P<0.05).Conclusions1.The plateau hypoxic environment has certain damage to the human auditory system,but with the increase in the time in Tibet,the hearing damage is reduced.2.The morphology of the cochlear HE staining of Wistar rats in the plains emigrating to the plateau changed after hypoxia;by adjusting the m RNA levels of AKT,m TORC1,TSC1,TSC2,PTEN,and p70S6 K in the auditory training in hypoxic environment by adjusting PI3 K / AKT signaling pathway Play a role.