Dapansutrile(OLT1177)alleviates radiation-induced intestinal injury
10.7644/j.issn.1674-9960.2025.09.001
- VernacularTitle:达泮舒腈(OLT1177)改善放射性肠损伤及机制研究
- Author:
Litao XU
1
;
Dongliang GUO
;
Weihao CI
;
Shensi XIANG
;
Xiaoming YANG
;
Guangming REN
Author Information
1. 军事科学院军事医学研究院,北京 100850
- Keywords:
dapansutrile(OLT1177);
radiation-induced intestinal injury;
nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome
- From:
Military Medical Sciences
2025;49(9):641-646
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of dapansutrile(OLT1177)in radiation-induced intestinal injury and the mechanism.Methods C57BL/6J mice were locally irradiated in the abdomen with 60Co to induce a model of radiation-induced intestinal injury.OLT1177 was intraperitoneally injected at a dose of 100 mg/kg 2 hours before irradiation and 6 hours after irradiation before the drug was administered once a day.At 12 hours after irradiation,intestinal tissues were taken for terminal deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining to detect apoptosis in intestinal tissues.At 4 days after irradiation,mouse serum was collected to detect the levels of inflammatory factors in the serum.Hematoxylin-eosin(HE)stainingwas used for the evaluation of the damage to the intestinal villus structure.Immunohistochemical staining was adopted to detect the changes in crypt proliferation in intestinal tissues.Finally,proteins were isolated from intestinal tissues,and Western blotting was employed to evaluate the activation of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome.Results After irradiation,the intestinal villi in mice were shortened.Meanwhile,there was a notable declinein the number of cells that were proliferating in the crypts,a surge in the number of apoptotic cells,and a significant spike in the overall inflammatory level.However,administration of OLT1177 inhibited the activation of the NLRP3 inflammasome,reduced apoptosis and pyroptosis,decreased the inflammatory level,and thus improved radiation-induced intestinal injury.Conclusion Administration of OLT1177 can significantly mitigate radiation-induced intestinal injury.
