PDCD4 By Autophagy Signaling Pathways In The Role Of Status Epilepticus In Mice And Its Mechanism

Introduction:Epilepsy is a common chronic brain disease that affects more than 65 million people worldwide and is caused by abnormal electrical discharges.Epilepsy attack frequently,can cause serious nerve dysfunction,but status epilepticus(SE)is one of the most serious neurological medical emergency epilepsy.The causes of SE involve many aspects,the main reasons may be the low blood concentration of antiepileptic drugs in chronic epilepsy patients,the occurrence of long-distance symptoms,the occurrence of cerebrovascular accidents,in the hypoxic body,and the metabolismor alcohol and drug withdrawal.The prognosis of SE is related to cause,age,duration of seizures,and response to treatment.Therefore,it is necessary to actively explore possible regulatory factors of epilepsy and explore the possible neuronal damage mechanismafter epileptic seizures,which may play an important role in the treatment and prognosis of epilepsy.Autophagy,the process by which cells "eat themselves",is a process by which cells self-degrade and recycle intracellular components.You can’t do without autophagy,but too much can be harmful.Therefore,autophagy is a tightly regulated process in all eukaryotes.Two ubiquitin-like systems,ATG8 and ATG12,are involved in the formation and maturation of autophagosomes.Mammalian target of rapamycin(mTOR)is a major regulator of autophagy.It receives a number of signaling pathways that sense the cell’s energy state to trigger or stop protein synthesis.It has been reported that inhibition of the PI3K/AKT/mTOR signaling pathway may accelerate cell apoptosis and autophagy.Programmed Cell Death 4(PDCD4)is a tumor suppressor gene,which affects Cell proliferation,apoptosis,transformation,invasion and autophagy.Meanwhile,studies have found that PDCD4 plays an important role in promoting the occurrence of inflammation.In the occurrence and development of cancer,obesity,diabetes and cardiovascular diseases.However,the role of PDCD4 in epilepsy is still unclear.In addition,PDCD4 can regulate autophagy as an upstreammolecule of autophagy pathway.Meanwhile,PDCD4 blocks the PI3K/AKT/mTOR pathway,which may inhibit the carcinogenic activity of cells.This suggests whether PDCD4 regulates the autophagy pathway and PI3K/AKT/mTOR pathway in SE.This suggests whether PDCD4 may regulate the autophagy pathway and PI3K/AKT/mTOR pathway in SE.This experiment aims to study the changes of autophagy signaling pathway,PI3 K,AKT and mTOR in mouse SE model after PDCD4 overexpression.In order to further understand the role of PDCD4 in SE.Methods:In this experiment,pilocarpine was injected intraperitoneally to induce epileptic state model,and C57 mice were randomly divided into 4 groups: normal control group,SE group,SE + control group,SE+ AAV-PDCD4 group,with 4 mice in each group.The expression levels of PDCD4,LC3,Beclin1,PI3 K,AKT and mTOR proteins in hippocampal tissues of different groups of mice and control group at 72 h after SE were detected by Western blot.Results:(1)Compared with the observation control group,the behavior of mice showed no significant change,while the epileptic group mice will soon appear seizures,manifested as a systemic convulsion,immediately into the epileptic state.(2)Compared with the control group,the latency of epilepsy in SE+AAV-PDCD4 group was significantly prolonged(P<0.05).(3)Compared to the control group,the expression of PDCD4 in the hippocampus of SE group increased after 72h(P<0.05).Compared to SE+ control virus group,THE expression of PDCD4 in SE+ AAV-PDCD4 group was significantly increased(P<0.05).(4)Compared to the control group,Beclin 1 and LC3II/I expression was increased in the hippocampus of SE group after 72h(P<0.05);Compared to SE+ control virus group,Beclin 1 and LC3II/I expression in SE+ AAV-PDCD4 group was significantly decreased(P<0.05).(5)Compared to the control group,the protein expressions of PI3 KAKT and mTOR in the hippocampus of SE group were increased after 72h(P<0.05);Compared to SE+ control virus group,the expressions of PI3 K,AKT and mTOR in SE+ AAV-PDCD4 group were significantly increased(P<0.05).Conclusion:(1)Overexpression of PDCD4 decreased the expression levels of Beclin 1 and C3II/I in hippocampus of pilocarpine-induced epilepsy model,and it was suspected that pdcd 4inhibited autophagy.(2)Overexpression of PDCD4 increased the expression levels of AKT,PI3 K,and mTOR in the hippocampal tissue of Pilocarpine induced epileptic state model,suggesting that PDCD4 may affect autophagy through PI3K/AKT/mTOR pathway.SE induced by Li Cl-pilocarpine,the expression level of PDCD4 in hippocampal tissues increased,and the trend of PDCD4 was basically consistent with that of autophagy and apoptosis,suggesting that PDCD4 may regulate autophagy and apoptosis signaling pathways;(3)Overexpression of PDCD4 prolonged the latency of epilepsy in mice.