Study on the mechanism of the action of mesenchymal stem cells in relieving radiation-induced lung injury in mice by inhibiting ferroptosis
10.3969/j.issn.1672-8270.2024.05.034
- VernacularTitle:间充质干细胞通过抑制铁死亡减轻小鼠放射性肺损伤的作用机制研究
- Author:
Xin TAN
1
,
2
;
Pei ZHANG
;
Lehui DU
;
Chuanbin XIE
;
Baolin QU
Author Information
1. 解放军总医院第一医学中心放射治疗科 北京 100853
2. 解放军医学院 北京 100853
- Keywords:
Mesenchymal stem cells(MSCs);
Radiation-induced lung injury;
Ferroptosis;
Oxidative stress
- From:
China Medical Equipment
2024;21(5):176-183
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the regulatory role of mesenchymal stem cells(MSCs)on radiation-induced lung injury in mice by the ferroptosis pathway.Methods:The mice were divided into normal control group,MSCs-treated group(MSCs group),single irradiation group(IR group)and IR combined with MSCs group(IR+MSCs group)according to random number table method before irradiation.A mouse model of radiation-induced lung injury was constructed using whole thorax irradiation with cobalt 60(60Co)(20Gy each time),and TNF-α and IL-6 levels of mouse were detected by enzyme-linked immunosorbent assay(ELISA).The injury of lung tissue in mice was assessed using hematoxylin eosin(HE)staining and Masson staining.Western Blot was used to examine the expression levels of ferroptosis-related proteins in lung tissue,including nuclear factor erythroid NF-E2 related factor 2(Nrf2),4-Hydroxynonenal(4-HNE)and glutathione peroxidase 4(GPX4).The expression level of prostaglandin-endoperoxide synthase 2 Gene(PTGS2)in the lung tissue of mice was detected by using quantitative polymerase chain reaction(qPCR),and the level of reactive oxygen species(ROS)in the lung tissue of mice was detected after radiation by using dihydroethidium(DHE),and the level of malondialdehyde(MDA)content in the lung tissue was detected after radiation.And then,the level of oxidative damage in the lung tissue of mice was assessed.Results:Elisa results showed the serum TNF-α and IL-6 levels in mice after irradiation in IR group were significantly higher than those in normal control group(F=53.60,10.65,P＜0.05),respectively.The HE and MSCs staining of pathological analysis showed that MSCs treatment could significantly relieve both early radiation-induced pneumonitis and advanced pulmonary fibrosis.After radiation,the 4-HNE expression level was upregulation and the Nrf2 expression level was downregulation in the lung tissues of mice,whereas MSCs were able to significantly reduce the 4-HNE expression and upregulate the Nrf2 expression.The mRNA expression level and MDA content of the ferroptosis gene PTGS2 were significantly increased,which were significantly higher than those of normal control group,while MSCs were able to significantly reduce its expression,and the differences were statistically significant(F=105.8,7.693,P＜0.05).Conclusion:MSCs is able to relieve significantly ionizing radiation-induced ferroptosis of lung epithelial cells,thereby relieve radiation-induced lung injury.
