Integrated Proteomic and Transcriptomic Analyses Reveal the Mechanisms Underlying the Organ-Protective Effects of Propofol Anesthesia in Infants Undergoing Living-Related Liver Transplantation

Background Hepatic ischemia-reperfusion injury (HIRI) during liver transplantation critically contributes to postoperative organ dysfunction. Although various anesthetics exhibit organ-protective properties, their molecular mechanisms remain unclear. Our previous study demonstrated that in infants undergoing living-related liver transplantation (LRLT), propofol-based total intravenous anesthesia (TIVA) attenuates HIRI, improving liver and kidney function and reducing severe complications. This study aimed to compare the molecular signatures underlying the effects of TIVA versus desflurane inhalation anesthesia on HIRI in LRLT using integrated transcriptomic and proteomic approaches. Methods In this prospective observational study, eight infants undergoing LRLT were grouped by the anesthetic regimen used intraoperatively: propofol-based TIVA ( n  = 4) or desflurane inhalation anesthesia ( n  = 4). Blood samples were collected preoperatively and at 2 hours post-reperfusion. Transcriptomic and proteomic analyses were performed to identify differentially expressed genes (DEGs) and proteins (DEPs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, along with integrated multi-omics analysis, were conducted. Serum levels of inflammatory cytokines were also measured before and after reperfusion in both groups. Results Transcriptomic analysis identified 145 differentially expressed genes (DEGs), which were primarily enriched in pathways related to antigen processing and presentation, regulation of cell signaling, and adaptive immune response. Proteomic analysis revealed 471 differentially expressed proteins (DEPs) involved in biological processes such as oxidative phosphorylation, T-cell differentiation, and immune and inflammatory responses. Integrated analysis identified six concordantly altered genes and proteins; further validation confirmed that transporter associated with antigen processing 1 (TAP1) was significantly upregulated at both the transcriptional and protein levels after reperfusion. Analysis of serum inflammatory cytokines showed that, compared with the desflurane group, the propofol group exhibited significantly lower levels of IL-6 and IL-8 and a significantly higher level of IL-10 after reperfusion. Conclusion Propofol-based TIVA confers superior protection against HIRI compared with desflurane inhalation anesthesia in infants LRLT, and its potential mechanisms may be related to modulation of immune responses, suppression of inflammatory pathways and reduction of apoptosis. The up-regulation of TAP1 represents a potential therapeutic target, providing a mechanistic rationale for optimizing anesthetic selection in pediatric LRLT.