军事医学2024，Vol.48Issue(5)：334-339,6.DOI:10.7644/j.issn.1674-9960.2024.05.03
达泮舒腈(OLT1177)减轻急性放射性肺损伤及机制初探
Dapansutrile(OLT1177)alleviates acute radiation-induced lung injury
摘要
Abstract
Objective To investigate the therapeutic effect and mechanism of NLRP3 inflammasome inhibitor-dapansutrile(OLT1177)-against acute radiation lung injury.Methods Mice were divided into the control group,OLT1177 injection group,irradiation group,and irradiation+OLT1177 injection group.A single dose of 22 Gy whole-lung 60Co radiation was used to establish a model of acute radiation lung injury.After 6 h of radiation,OLT1177(100mg/kg,once daily)was administered intraperitoneally.After 14 consecutive days of administration,lung tissues were collected and weighed while the lung coefficient was calculated.Hematoxylin-eosin(HE)staining and F4/80 immuno-histochemical staining were used to observe the pathological changes and inflammatory cell infiltration in lung tissues.Real-time quantitative PCR(qPCR)was used to detect the transcription levels of NLRP3,IL-1β,and other mRNAs in lung tissues.Serum cytokines such as TNF-α and IL-6 were measured by cytometric bead array(CBA).The activation of Caspase-1 and IL-18 was detected by Western blotting.Results Radiation caused acute inflammation in the lung tissues of mice,manifested as edema in the lung tissues and destruction of the alveolar structure,increased macrophage infiltration,and elevated expressions of inflammatory genes NLRP3,IL-1β,TNF-α,and IL-6 in the lung tissues and higher serum levels of TNF-α,IL-6.Treatment with OLT1177 significantly improved the above symptoms induced by radiation.OLT1177 inhibited the activation of NLRP3 inflammasome downstream Caspase-1 and IL-18 induced by radiation.Conclusion OLT1177 can significantly alleviate acute radiation lung injury in mice,which may be due to its inhibition of NLRP3 inflammasome activation induced by radiation.关键词
达泮舒腈(OLT1177)/急性放射性肺损伤/NLRP3炎症小体/Caspase-1活化Key words
dapansutrile(OLT1177)/acute radiation lung injury/NLRP3 inflammasome/Caspase-1 activation分类
医药卫生引用本文复制引用
慈维昊,李亚婷,徐立涛,陈晨,杨晓明,任广明..达泮舒腈(OLT1177)减轻急性放射性肺损伤及机制初探[J].军事医学,2024,48(5):334-339,6.基金项目
北京市科技新星基金项目(2022039) （2022039）
