目的:有人担心COVID-19患者会出现肺纤维化。使用鼠标模型,我们比较了注射SARS-CoV-2刺突蛋白(COVID-19)后的肺部炎症与辐射诱导的炎症,以证明两种模型之间的相似性.SARS-CoV-2(COVID-19)诱导炎症细胞因子和应激反应,这在电离辐射引起的急性肺损伤中也很常见。细胞衰老,这是暴露于SARS-CoV-2和辐射后的后期效应,被调查。
方法:我们评估了SARS-CoV-2刺突蛋白与电离辐射对K18-hACE2小鼠肺的影响,人肺细胞系,和新移植的人肺。我们测量了活性氧,DNA双链断裂,刺激转化生长因子-β途径,和暴露于SARS-CoV-2刺突蛋白后的细胞衰老,照射或SARS-COV-2和照射。我们还测量了辐照或暴露于SARS-CoV-2后抗氧化剂辐射缓解剂MMS350的作用。
结果:SARS-CoV-2刺突蛋白诱导活性氧,DNA双链断裂,转化生长因子-β信号通路,和衰老,之前或之后的电离辐射加剧了这种情况。水溶性辐射对策,MMS350,减少了刺突蛋白诱导的变化。
结论:在SARS-Co-2和辐射小鼠模型中,观察到类似的反应,表明照射或暴露于SARS-CoV-2病毒可能导致类似的肺部疾病,例如肺纤维化.照射和SARS-CoV-2的组合可能导致更严重的肺纤维化病例。细胞衰老可以解释暴露于SARS-CoV-2尖峰蛋白和电离辐射的一些后期影响。
OBJECTIVE: There is concern that people who had COVID-19 will develop pulmonary fibrosis. Using mouse models, we compared pulmonary inflammation following injection of the spike protein of SARS-CoV-2 (COVID-19) to radiation-induced inflammation to demonstrate similarities between the two models. SARS-CoV-2 (COVID-19) induces inflammatory cytokines and stress responses, which are also common to ionizing irradiation-induced acute pulmonary damage. Cellular senescence, which is a late effect following exposure to SARS-CoV-2 as well as radiation, was investigated.
METHODS: We evaluated the effect of SARS-CoV-2 spike protein compared to ionizing irradiation in K18-hACE2 mouse lung, human lung cell lines, and in freshly explanted human lung. We measured reactive oxygen species, DNA double-strand breaks, stimulation of transforming growth factor-beta pathways, and cellular senescence following exposure to SARS-CoV-2 spike protein, irradiation or SARS-COV-2 and irradiation. We also measured the effects of the antioxidant radiation mitigator MMS350 following irradiation or exposure to SARS-CoV-2.
RESULTS: SARS-CoV-2 spike protein induced reactive oxygen species, DNA double-strand breaks, transforming growth factor-β signaling pathways, and senescence, which were exacerbated by prior or subsequent ionizing irradiation. The water-soluble radiation countermeasure, MMS350, reduced spike protein-induced changes.
CONCLUSIONS: In both the SARS-Co-2 and the irradiation mouse models, similar responses were seen indicating that irradiation or exposure to SARS-CoV-2 virus may lead to similar lung diseases such as pulmonary fibrosis. Combination of irradiation and SARS-CoV-2 may result in a more severe case of pulmonary fibrosis. Cellular senescence may explain some of the late effects of exposure to SARS-CoV-2 spike protein and to ionizing irradiation.