Propionate intervenes mast cell function to alleviate intestinal ischemia-reperfusion injury by regulating AhR/Notch1...

Intestinal ischemia-reperfusion (II/R) has an insidious onset but rapid progression, in which activation of intestinal immune cells and release of inflammatory factors play an important role. However, there is no clear therapeutic drug or method for II/R injury. Short-chain fatty acids (SCFAs) including propionate produced by the catabolism of intestinal flora have important intestinal protective effects and help prevent related diseases. This study aimed to investigate the protective effects of propionate (PR) in II/R injury.

A combination of bioinformatics and experimental validation was used to analyze the targets of propionate action on II/R injury. The effects of PR on mast cells were evaluated by analyzing the expression of inflammatory factors and trypsin, as well as flow cytometry. The effect of PR on II/R injury was evaluated by survival rate, histology, immunohistochemistry, immunofluorescence and TUNEL.

PR can participate in the process of II/R injury through multiple targets. PR has a strong binding ability with Aryl hydrocarbon receptor (AhR)(-3.5 kcal/mol). In addition, PR inhibited the activation of mast cells during the II/R process by increasing the expression of AhR, thereby inhibiting the inflammatory response, reducing intestinal mucosal damage, and enhancing the expression of tight junction proteins, thereby alleviating II/R injury in mice.

This study demonstrated that PR, a metabolite of intestinal flora, inhibited mast cell activation by regulating the AhR-Notch1 pathway, thereby attenuating intestinal ischemia-reperfusion injury.