基于4D-DIA技术研究表柔比星所致化疗相关认知障碍机制OACSTPCD

Objective To investigate the mechanism of chemotherapy-induced cognitive impairment(CICI)caused by Epirubicin us-ing the four-dimensional data-independent acquisition(4D-DIA)proteomics technology.Methods An in vitro blood-brain barrier(BBB)model was established using bEnd.3 mouse brain microvascular endothelial cells,and then randomly divided into Epirubicin group and blank control group.The cells in Epirubicin group were treated with 5 μmol/L epirubicin for 24 h,while the cells in blank control group were not given any intervention.Differential protein expression between the two groups was detected and compared using 4D-DIA technology.The differential proteins were analyzed by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and a protein-protein interaction(PPI)network was constructed.Results A total of 1 282 differential proteins were identi-fied between the two groups,including 378 upregulated proteins and 904 downregulated proteins.GO analysis revealed that differen-tial proteins were mainly enriched in the intracellular compartment and involved in biological processes such as biological regulation,organic substance metabolism,and cellular metabolism,and were associated with molecular functions such as binding and catalysis.KEGG pathway analysis indicated interactions of differential proteins with spliceosomes,RNA polymerases,and mRNA surveillance pathways.PPI network analysis highlighted central proteins including TP53,RNA helicase DHX15,and small nuclear ribonucleopro-tein D3,which are related to apoptosis and spliceosome functions.Conclusion Epirubicin may induce CICI by disrupting the spli-ceosome function and affecting normal connectivity and transport systems in brain microvascular endothelial cells.