Abstract
Ferroptosis is a death mode centered on iron metabolism and lipid peroxidation pathways. Recent studies have shown that inhibiting ferroptosis can alleviate intestinal ischemia/reperfusion (II/R) injury. Hydrogen (H2) can mitigate II/R injury by anti-oxidative stress, while Silicon (Si)-based agent can generate a large amount of H2 in the alkaline environment of the intestine during II/R. However, it is unclear whether Si-based agent can alleviate II/R injury. By establishing a mouse model of II/R injury, we examined the histopathological changes, apoptosis, inflammatory factors, oxidative stress, and ferroptosis levels in the small intestine. We found that the AMPK-Sirt1 pathway is activated in the small intestine of mice after II/R, and Si-based agent can further activate this pathway, alleviating intestinal injury, inhibiting apoptosis, reversing inflammation and oxidative stress, and suppressing ferroptosis in mice after II/R. Furthermore, by administering AMPK agonists and inhibitors, as well as ferroptosis inhibitors for further exploration, we discovered that the hydrogen generated by Si-based agent may inhibit ferroptosis and alleviate II/R injury through the AMPK-Sirt1 signaling pathway. This study provides theoretical and experimental evidence for elucidating the pathogenesis of intestinal ischemia/reperfusion injury and for the clinical application of Si-based agent.
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This study was supported by a grant from the Zigong Key Science and Technology Program (Grant No. 2023YLWS16), and partly by grants from the Health Commission of Sichuan Province Medical Science and Technology Program (Grant No. 25CXTD10) and the Zigong Key Science and Technology Program—Zigong Academy for Medical Big Data and Artificial Intelligence Joint Project (Grant No. 2023-YGY-2-01).
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Liu, X., Wang, B., Wang, X. et al. Silicon-based agent alleviating intestinal ischemia/reperfusion injury in mice by inhibiting ferroptosis via activating AMPK-Sirt1 signaling pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-52405-x
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DOI: https://doi.org/10.1038/s41598-026-52405-x
