Objective To investigate the protective effect of dimethyl fumarate(DMF)on irradiation(IR)-induced intestinal damage and the underlying mechanism.Methods 60Co γ ray irradiator was used to induce radiation injury in mice.Small intestines were collected after irradiation and subjected to H&E and TUNEL staining to detect the pathological changes and apoptosis in situ.Inflammatory response was determined by quantifying levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18),tumor necrosis factor-α(TNF-α),NOD-like receptor protein 3(NLRP3)or melanoma deficiency factor 2(AIM2)in intestine with enzyme-linked immunosorbent assay.Western blot and immunofluorescence staining were used to detect the expression of NLRP3 and AIM2 in small intestine.To verify the essential role of NLRP3 and AIM3 on radio-protective of DMF on small intestine,the selective agonists were employed.Results DMF(15 mg·kg-1)significantly improved the pathological status of small intestine and decreased the apoptosis level of intestinal cells upon whole body IR exposure.DMF could also significantly inhibit the inflammatory response on small intestine induced IR injury.Western blot results and tissue immunofluorescence staining showed that DMF could significantly suppress the upregulation of NLRP3 and AIM2.With selective agonists,the radio-protective effect of DMF on small intestine was diminished,indicating the critical role of NLRP3 and AIM2 inflammasome signaling involved in the anti-radiation activity of DMF.Conclusion DMF is a promising agent to alleviate IR-induced intestinal injury,and the inhibition of NLRP3/AIM2 inflammasome signaling seem to be the underlying mechanism involved in the radio-protective effect of DMF.
维普
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