军事医学2025，Vol.49Issue(8)：569-575,7.DOI:10.7644/j.issn.1674-9960.2025.08.002
敲除核苷酸结合寡聚化结构域样受体蛋白3改善放射导致的早期肺炎和晚期肺纤维化
Nucleotide-binding oligomerization domain-like receptor protein 3 knockout improves radiation-induced pneumonia and pulmonary fibrosis
摘要
Abstract
Objective To construct nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)knockout mice in order to investigate the effects of NLRP3 knockout on radiation-induced acute pneumonitis and pulmonary fibrosis.Methods Nlrp3+/+and Nlrp3-/-mice were randomly divided into the control group and irradiation group.To induce radiation-caused acute pneumonitis,the control group was exposed to sham irradiation while the irradiation group was exposed to 60Co γ-rays at a dose of 22 Gy at a dose rate of 184.30 R/min.At 14 days post-irradiation,the body weight of each mouse and the wet weight of its lung tissue were measured separately using an analytical balance to calculate the lung coefficient.Quantitative real-time PCR(qPCR)and cytometric bead array(CBA)were used to detect inflammatory responses in lung tissues and serum.Hematoxylin-eosin(HE)staining and F4/80 immunohistochemical staining were used to assess pathological changes and inflammatory cell infiltration in lung tissues.Cysteinyl aspartate specific proteinase-1(caspase-1)activation was analyzed by Western blotting.To establish a model of radiation-induced pulmonary fibrosis,mice were irradiated with 60Co γ-rays at a dose of 18 Gy at a dose rate of 174.67 R/min.At 24 weeks post-irradiation,HE staining and Masson staining were performed to evaluate pulmonary fibrosis.Results NLRP3 knockout inhibited caspase-1 activation,reduced inflammatory responses in lung tissues and serum,suppressed macrophage infiltration,alleviated pulmonary edema,and thereby protected against acute radiation-induced lung injury.Additionally,NLRP3 knockout significantly ameliorated late-stage radiation-induced pulmonary fibrosis.Conclusion NLRP3 knockout can mitigate both early radiation-induced pneumonia and lateradiation-induced pulmonary fibrosis.关键词
核苷酸结合寡聚化结构域样受体蛋白3炎症小体/敲除/急性放射性肺损伤/肺纤维化Key words
nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome/knockout/acute radiation lung injury/pulmonary fibrosis分类
医药卫生引用本文复制引用
陈晨,徐立涛,尹栩,慈维昊,向慎思,杨晓明,任广明..敲除核苷酸结合寡聚化结构域样受体蛋白3改善放射导致的早期肺炎和晚期肺纤维化[J].军事医学,2025,49(8):569-575,7.基金项目
北京市科技新星基金项目(2022039) （2022039）
