Network Pharmacology Prediction And Molecular Docking-based Strategy To Explore The Mechanism Of Dexmedetomidine Against POCD

Objective: Using network pharmacology and molecular docking technology,dexmedetomidine was predicted to act on the hub targets and signaling pathways of postoperative cognitive dysfunction(POCD),and then its mechanism of action was explored.Methods: Drug Bank,Swiss Target Prediction,Target Net,Super Pred,and Therapeutic Target Database(TTD)were searched and obtained dexmedetomidine drug-related targets.Search and obtain POCD disease target genes in the databases Gene Cards,OMIM,and Dis Ge NET respectively.The online tool Venny 2.1.0 was used to intersect drug targets and disease target genes to obtain the potential target of dexmedetomidine acting on POCD.The STRING database was used to analyze the intersection targets and their interaction relationships,construct a protein-protein interaction network(PPI)and screen out the hub targets.Visualize PPI analysis results with Cytoscape software;Using the cyto Hubba tool,the top 10 targets in terms of screening degree value(Degree)are used as hub targets.Enrichment analyses using intersecting targets,including Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG),were used to reveal the potential mechanism of action of dexmedetomidine to improve POCD.Use Cytoscape software to build a drug-hub target-pathway-disease network to visualize its process of action.The hub target was used as the receptor and dexmedetomidine as the ligand,and the molecular docking was performed with Autodock software to verify the results;Finally,the molecular docking results with the lowest binding energy were visualized by Py MOL software.Results: Finally,282 dexmedetomidine drug-related genes,2262 POCD disease target genes and 138 intersection genes were screened.The intersecting genes were constructed to construct PPI networks,ranked by degree value,and the top 10 hub targets were screened as follows: HSP90AA1、SLC6A4、SLC6A3、GRIN2B、CYP3A4、MAOA、NOS3、RELA、NR3C1、MAOB.A total of 1486 results were obtained in GO functional enrichment analysis,mainly involving biological processes: cellular response to nitrogen compound、cellular response to organic cyclic compound、circulatory system process、blood circulation、response to xenobiotic stimulus、synaptic signaling synaptic signaling,etc.The main cellular components involved include: postsynaptic membrane、integral component of synaptic membrane、dendrite、membrane raft,etc.Molecular functions are mainly involved: G protein-coupled amine receptor activity、neurotransmitter receptor activity、heme binding、G protein-coupled serotonin receptor activity、Steroid hydroxylase activity、monooxygenase activity、protein serine/threonine/tyrosine kinase activity、postsynaptic neurotransmitter receptor activity,etc.A total of 170 pathways were obtained in the KEGG pathway enrichment analysis,mainly involving: neuroactive ligand-receptor interaction、calcium signaling pathway、serotonergic synapse、PI3K-Akt signaling pathway、dopaminergic synapse、c AMP signaling pathway、apoptosis、pathways of neurodegeneration-multiple diseases、HIF-1 signaling pathway,etc.The molecular docking results showed that dexmedetomidine had good binding ability to the above 10 hub targets.Conclusion:In this study,network pharmacology and molecular docking technology were used to predict that DEX may act on HSP90AA1 and NOS3,regulate HSP90/Akt,PI3K-Akt,NF-κB signaling pathways,reduce neuroinflammation and neuronal apoptosis,and improve POCD.DEX may also act on SLC6A4,SLC6A3,MAOA,MAOB,GRIN2 B,regulate c AMP signaling pathway,NF-κB signaling pathway,regulate neurotransmitters,and improve POCD.