The Neuroprotective Effect Of Prohibitin And Its Underlying Mechanism In Cerebral Ischemia Injury

Objective: The aim of this study is to investigate DEGs(Differentially expressed genes)after ischemic stroke by bioinformatics,and to explore the target genes and specific mechanism of ischemic stroke.Methods: The GSE1357 expression profiles was downloaded from GEO database,and the DEGs were screened out after R language.The key target genes were screened by DAVID database and PPI(Protein–protein interaction)network analysis.Subsequently,the changes of PHB1 were verified in animals,primary neurons and SH-SY5 Y cells.Finally,TTC staining,FJC staining,CCK8 and edema measurement were used to verify the effect of PHB1 on ischemic stroke.Results: We obtained 82 DEGs from GSE1357 profiles,including 66 down-regulated DEGs and 16 up-regulated DEGs.GO analysis results suggested that the DEGs primarily participate in positive regulation of gene expression,central nervous system development,response to lipopolysaccharide,viral entry into host cell,and response to ethanolin the BP terms,and the KEGG pathways are mainly enriched in oxidative phosphorylation,parkinson's disease,and cocaine addiction.Through PPI network analysis,we confirmed 6 candidates and selected PHB1 for further study.After MCAO,we found that PHB1 increased in the first 3 hours and then decreased in the both the white matter and the gray matter regions.After OGD,we found that PHB1 decreased from the beginning in the primary neurons.TTC staining showed that PHB1 could effectively reduce the infarct area(P < 0.01).FJC and the detection of brain water content obtained the same results that compared with the MACO + LV group,the number of deformed neurons and the degree of edema were significantly reduced in the MCAO + PHB1 group(P < 0.01).In vitro,CCK8 results showed significantly increased cell activity in OGD + PHB1 group(P < 0.01).Conclusion: There is a certain relationship between PHB1 and ischemic stroke.In a very short period of time,the expression level of PHB1 increases and then presents a decreasing trend.Moreover,PHB1 can effectively protect brain tissues by reducing edema and other mechanisms.Significance: After ischemic stroke,neuron as important cell is unrecoverable and organization drug effects are not significant.So,looking for new targets for the treatment of damaged neurons is extremely urgent.