军事医学2025,Vol.49Issue(9):641-646,6.DOI:10.7644/j.issn.1674-9960.2025.09.001
达泮舒腈(OLT1177)改善放射性肠损伤及机制研究
Dapansutrile(OLT1177)alleviates radiation-induced intestinal injury
摘要
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.关键词
达泮舒腈(OLT1177)/放射性肠损伤/核苷酸结合寡聚化结构域样受体蛋白3炎症小体Key words
dapansutrile(OLT1177)/radiation-induced intestinal injury/nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome分类
医药卫生引用本文复制引用
徐立涛,郭栋梁,慈维昊,向慎思,杨晓明,任广明..达泮舒腈(OLT1177)改善放射性肠损伤及机制研究[J].军事医学,2025,49(9):641-646,6.基金项目
北京市科技新星基金项目(2022039) (2022039)