Radiation enteritis is a common complication of abdominal irradiation (IR) therapy. However, the molecular mechanism of radiation enteritis accompanied by impaired intestinal barrier function is not clear. The aim of this study was to investigate the important role of autophagy in radiation-induced intestinal barrier function impairment. IR increased the abundance of autophagy-related genes in the colonic mucosa of mice. An autophagy activator (rapamycin) inhibited the oxidative stress (reactive oxygen species, reactive nitrogen species, malondialdehyde, and hydrogen peroxide) and inflammatory response (interleukin-1β, -6, -8, and tumor necrosis factor-α) in the colon samples. Antioxidant indices (superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity) in serum and colonic mucosa were significantly increased in the rapamycin group. Rapamycin can improve the activity of mitochondrial respiratory chain complexes I-V in colon mucosa. In addition, rapamycin reduced the gene expression and enzyme activity of caspase in the colonic mucosa. Levels of endotoxin, diamine peroxidase, d-lactic acid, and zonulin in serum and colonic mucosa were significantly reduced in the rapamycin group. Moreover, rapamycin significantly elevated the gene abundance of zonula occludens-1, occludin, claudin-1, and claudin-4. In contrast, completely opposite results were obtained for the autophagy inhibitor 3-methyladenine as compared to those of rapamycin. These results revealed that inhibition of autophagy is an important mechanism of intestinal barrier function damage caused by radiation. Collectively, these findings increase our understanding of the pathogenesis of radiation-induced intestinal barrier dysfunction.
Copyright © 2020 American Chemical Society.