Ionomics and proteomics analysis of the pancreatic repair in a murine severe acute pancreatitis model treated with Qingyi decoction

<h4>Background</h4>Current therapeutic options for severe acute pancreatitis (SAP) remain limited. The integration of traditional Chinese and Western medicines offers a promising approach for patients with SAP, with Qingyi decoction (QYD) emerging as a classic and effective formula for this condition. Nevertheless, its precise mechanism-particularly regarding ionomics and proteomics-requires further elucidation.<h4>Purpose</h4>This study aimed to investigate the possible underlying mechanisms by exploring the characteristics and relationships of alterations in ionomics and proteomics profiles during pancreatic repair in a mouse model of SAP treated with QYD.<h4>Methods</h4>The therapeutic efficacy of QYD in SAP was validated through pathological section analysis and immunohistochemistry. Total elemental analysis of serum and mouse tissues was performed using inductively coupled plasma-mass spectrometry to identify relevant target elements. XPS analysis was employed to determine the chemical speciation of the target elements. Proteomic analysis, combined with KEGG, GO enrichment and STRING protein-protein interaction analyses, elucidated the protein molecules and biological pathways and the core proteins involved in QYD-mediated SAP treatment were verified by Western blotting. Finally, to clarify the relationship between changes in ion content and alterations in oxidative phosphorylation-related proteins and mitochondria-associated proteins, we conducted Pearson correlation analysis and mitochondrial morphological identification.<h4>Results</h4>QYD effectively alleviated symptoms of lipopolysaccharide-induced SAP. During this process, metal ions-particularly zinc ions-underwent significant coordination changes. Five core proteins were extracted from the proteomics section, and oxidative phosphorylation emerged as a critical pathway in this therapeutic mechanism. Furthermore, correlation analysis revealed close connections between ionic changes (Zn, Cu, Fe, Ca, Mg, Mn, and Se) and the expression profiles of oxidative phosphorylation-related proteins (Nduf and Atp5f1b) and mitochondrial-associated proteins (Tfam, Ppp3ca, and Myef2), which were also consistent with the observed changes in mitochondrial morphology.<h4>Conclusion</h4>The therapeutic mechanism of QYD in SAP may involve the ionic spectrum, especially zinc, modulating disease progression through mitochondrial oxidative phosphorylation.