Nucleotide-binding oligomerization domain-like receptor protein 3 knockout improves radiation-induced pneumonia and pulmonary fibrosis
10.7644/j.issn.1674-9960.2025.08.002
- VernacularTitle: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
- Author:
Chen CHEN
1
;
Litao XU
;
Xu YIN
;
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:
nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome;
knockout;
acute radiation lung injury;
pulmonary fibrosis
- From:
Military Medical Sciences
2025;49(8):569-575
- CountryChina
- Language:Chinese
-
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.
