川芎嗪缓解顺铂神经毒性的作用及机制研究OA

Cisplatin is frequently accompanied by dose-dependent peripheral neurotoxicity in clinical practice,and there is a lack of ideal protective agents.Ligustrazine possesses prominent neuroprotective activity.In this paper,network pharmacology was em-ployed to investigate the potential mechanism by which ligustrazine prevents cisplatin-induced neurotoxicity.Ligustrazine targets were obtained from the SwissTarget Prediction and Comparative Toxicogenomics Database(CTD).Targets associated with cisplatin and neurotoxicity were screened using the GeneCards,CTD,and Online Mendelian Inheritance in Man Databases(OMIM).Protein-protein interaction(PPI)analysis was conducted via the STRING database to identify key targets.Gene Ontology(GO)and Kyoto Enycyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the Hiplot platform.Validation was car-ried out through molecular docking and in vitro experiments,including Cell Counting Kit-8 assay(CCK-8),Real-time Quantitative Polymerase Chain Reaction(RT-qPCR),and Enzyme-Linked Immunosorbent Assay(ELISA).The results show that a total of 93 li-gustrazine targets,11 123 cisplatin-related targets,and 23 673 neurotoxicity-related targets were retrieved,with 84 overlapping tar-gets.Enrichment analysis revealed that these targets were involved in 3 698 biological processes,361 molecular functions,236 cellu-lar components,and 234 signaling pathways.Molecular docking demonstrated that ligustrazine exhibited binding energies below-4 kcal/mol with Interleukin-6(IL-6),Tumor Necrosis Factor(TNF),and Hypoxia-Inducible Factor 1 Alpha(HIF1A).In vitro ex-periments confirmed that ligustrazine significantly increased the viability of cisplatin-damaged neuronal cells(P＜0.05)and down-regulated both mRNA and protein expression levels of TNF,IL-6,and HIF1A(P＜0.05).Ligustrazine likely exerts therapeutic ef-fects against cisplatin-induced neurotoxicity by inhibiting core targets such as IL-6,TNF,and HIF1A,modulating IL-17,HIF1A,and TNF signaling pathways,and thereby alleviating inflammatory and oxidative stress responses.