Purpose Severe acute pancreatitis (SAP) is a life-threatening condition characterized by rapid progression and high mortality. While colchicine has shown potential in mitigating SAP-related inflammation, its underlying mechanisms remain unclear. This study aimed to explore the molecular mechanisms by which colchicine alleviates SAP in rats through comprehensive transcriptomic and bioinformatics analyses. Methods Transcriptomic sequencing was performed on pancreatic tissues from control (CON), SAP, and colchicine-treated (SAP+COL) rat groups. Differential gene expression analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to identify key pathways. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through topological analysis. The expression of hub genes was validated via qRT-PCR and immunohistochemistry (IHC). Immune cell infiltration was analyzed using the xCELL algorithm, and correlations between hub genes and immune cells were assessed. Results The study identified seven hub genes associated with colchicine’s protective effects: IL-6, Mmp9, Hif1a, Timp1, Mpo, Lcn2, and Thbs1. Colchicine significantly reduced the infiltration of macrophages and neutrophils in SAP tissues while increasing CD8+ T cell infiltration. Notably, Hif1a and Thbs1 showed strong positive correlations with macrophage and neutrophil infiltration, whereas Mmp9 exhibited a negative correlation with CD8+ T cell infiltration. GO and KEGG analyses revealed that these genes are involved in inflammatory and immune-related pathways, such as the TNF, NF-κB, and IL-17 signaling pathways. Conclusion Colchicine alleviates SAP by modulating the expression of key genes related to inflammation and immune response, particularly through its effects on macrophage, neutrophil, and CD8+ T cell dynamics. The identified hub genes (IL-6, Mmp9, Hif1a, Timp1, Mpo, Lcn2, and Thbs1) represent potential therapeutic targets for SAP, with Hif1a, Thbs1, and Mmp9 playing critical roles in immune cell regulation. These findings provide a theoretical basis for the clinical application of colchicine in SAP treatment.

Acute Severe Pancreatitis, Colchicine, Bioinformatics, Protein-Protein Interaction, Immune Cell Infiltration