The Improvement of Experimentally Induced Gastric Ulcers in Rats by Inhibiting Vascularization Through the Blocking of the TNF-α Type 1 Receptor.

BACKGROUND

About 5%-10% of the world's population is affected by gastric ulcers, which can result in gastrointestinal perforation and bleeding. Consequently, we aimed to investigate whether blocking TNF-α type 1 receptor (TNFR1) with CAY10500 could diminish experimentally induced gastric ulcer (GU) in rats by modulating vascularization.

METHODS

Rats were administered with a single oral dose of 80 mg/kg of indomethacin to produce gastric ulcers. Subsequently, some rats were given 1 mg/kg of CAY10500 orally. Gastric samples were used to assess the genetic expression and protein levels of TNFR1, VEGF, ERK, PI3K, AKT (also known as PKB), and ICAM-1. Gastric sections underwent electron microscopic examination and were subjected to hematoxylin and eosin staining and immunostaining using anti-TNFR1, anti-VEGF, and anti-ICAM-1 antibodies.

RESULTS

CAY10500 demonstrated the ability to inhibit the expression of TNFR1. Examination of micro-images of GU using electron microscopy or H/E staining revealed extensive necrosis, resulting in the complete loss of regular ultrastructural features of epithelial nuclei and cytoplasmic organelles, as well as the loss of tight junctions and disruption of cell membranes. Significantly, the administration of CAY10500 mitigated these effects. Furthermore, CAY10500 significantly elevated the expressions of VEGF, ERK, PI3K, and AKT, which was associated with a significant reduction in the expression of ICAM-1.

CONCLUSION

CAY10500 effectively improved experimentally induced GU in rats. It works by inhibiting TNFR1 and activating angiogenesis and cell proliferation pathways, leading to gastric tissue healing. CAY10500 significantly reduced the adhesion molecule pathways.