OBJECTIVE To identify key factors involved in the regulation of hypoxia-induced inflammation-related signaling pathways using a combination of bioinformatics methods and experiments. METHODS A cellular model of hypoxia-induced hippocampal neuronal damage was prepared by treating mouse hippocampal neuronal HT22 cells with CoCl2. The cells were then collected for transcriptome sequencing. Based on the sequencing results,key molecules were identified using differential analysis,gene ontology(GO) function and Kyoto Encyclopedia of Genomes(KEGG) pathway analysis,and protein-protein interaction network(PPI) analysis. The effects of key molecules on cells were investigated. RESULTS Differential analysis revealed a total of 8975 differential genes,which were subjected to GO and KEGG analysis. KEGG analysis revealed that these genes were involved in signaling pathways such as pancreatic cancer,EGFR tyrosine kinase inhibitor resistance,animal mitosis,base excision repair,and chronic myeloid leukemia. PPI networks were constructed for genes enriched in these pathways,and the MCC algorithm screened the top 5 key genes,which were shown to be HRAS,KRAS,PTEN,VEGFA,and SRC. HRAS and VEGFA were selected for subsequent experiments,and the results showed that after CoCl2 treatment,the viability of HT22 cells was significantly decreased(P<0.05),HRAS was significantly down-regulated and VEGFA was significantly up-regulated in CoCl2-treated cells(P<0.05),the levels of TNF-α,IL-1β,and IL-6 were significantly increased(P<0.001). However,treatment with overexpression of HRAS or low expression of VEGFA led to an increase in the activity of cell growth(P<0.05) as well as a significant decrease in TNF-α,IL-1β,and IL-6 levels(P<0.001). CONCLUSION In sleep apnea,HRAS or VEGFA may lead to cognitive impairment by affecting inflammatory factors.