Effects of Mast Cells Induced by NSAIDs Impair Intestinal Epithelial Barrier Function In Vivo and In Vitro.

To explore the correlation between altered expression of mast cells and PAR-2 and impaired mucosal barrier in NSAIDs enteropathy through animal and cell experiments, and to elucidate the role of mast cells and PAR-2 in the pathogenesis of NSAIDs enteropathy and the regulatory mechanism of the tight junction of intestinal epithelium. Animal experiments: the NSAIDs-related small intestine injury model was established by intragastric administration of diclofenac sodium, and mast cells were detected by toluidine blue staining. Cell experiments: Intestinal epithelial cell line (IEC-6) was applied with diclofenac sodium and its activity was detected by CCK-8.IEC-6 and RBL-2H3 were co-cultured to evaluate the permeability of intestinal epithelial cells by detecting the concentration of potassium ion and LDH. The expressions of tight junction proteins (zo-1, claudin-1, occludin), cytoskeletal components (actin, tubulin, keratin) and par-2 were analyzed by Western Blot. In animal experiments, the number of mast cells was significantly increased after 24 h of action of diclofenac sodium. In cell experiments, the survival rate of IEC-6 cells decreased significantly when the concentration of diclofenac sodium is more than 50 μg/mL; after 24 h of co-culture, the potassium and LDH concentration in the co-culture group were significantly higher, and the expression of ZO-1, claudin-1, occludin, tubulin, and keratin was decreased. Mast cells activate PAR-2 in intestinal epithelial cells, downregulate the related proteins of cell tight junctions and cytoskeletal proteins, and increase the permeability of intestinal epithelial cells.