Abstract
Intestinal ischemia-reperfusion (II/R) injury is a significant clinical concern with high mortality rates. Mitochondria play a crucial role in this process, and maintaining mitochondrial homeostasis is a potential treatment target. SENP1 is a de-SUMOylated hydrolase that may regulate SIRT3, a major mitochondrial deacetylase. However, the role of SENP1 and SIRT3 in II/R remains unclear. Employing a combination of in vitro cell culture experiments utilizing Caco-2 cells and in vivo II/R models with SD rats, along with an array of molecular biology techniques such as gene silencing, protein detection methods, immunoprecipitation, histological analysis, and functional assays, this study delved into the role of SENP1 and SIRT3 in intestinal ischemia-reperfusion injury. Statistical analysis was meticulously conducted to evaluate the significance of the obtained results. SENP1 and SIRT3 are co-expressed and interact in Caco-2 cells. In models of II/R, the expression of SENP1 increased while that of SIRT3 decreased. Reducing SENP1 expression by siRNA or enteral nutrition intervention with bupropion alleviated intestinal II/R injury, reduced mitochondrial damage and oxidative stress, and improved the number and function of mitochondria. Our study demonstrates the importance of SENP1 and SIRT3 in intestinal ischemia-reperfusion injury. Reducing SENP1 expression through siRNA or enteral nutrition intervention shows promise as a potential therapeutic approach. This research provides new insights into the mechanism of II/R injury and paves the way for further investigations.