Protective effect of heme oxygenase-1 inhibiting M1 macrophage polarization on seawater-drowning-induced lung injury in mice
10.3760/cma.j.cn311847-20201119-00431
- VernacularTitle:血红素加氧酶-1抑制M1巨噬细胞极化对海水淹溺性肺损伤小鼠的保护作用
- Author:
Binbin WAN
1
;
Gang LIU
1
;
Jianing YUAN
1
;
Junjie HU
1
;
Minying WANG
1
;
Duo DING
1
;
Yaxian WU
1
;
Dan CHEN
1
;
Qingfeng PANG
1
Author Information
1. 214122 江苏省无锡，江南大学无锡医学院
- Publication Type:Journal Article
- Keywords:
HO-1;
Seawater drowning;
Lung injury;
Macrophage polarization
- From:
Chinese journal of nautical medicine and hyperbaric medicine
2021;28(3):350-355
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and significance of heme oxygenase-1 (HO-1) in regulating macrophage polarization on seawater-drowning-induced acute lung injury (ALI) in mice.Methods:Raw 264.7 cells were divided into four groups. The control group was not stimulated with artificial seawater (SW), while the SW 8 h group, SW 24 h group, and SW 72 h group stimulated with artificial seawater for 8 h, 24 h, and 72 h, respectively. The morphological changes of cells were observed, the apoptosis, the contents of inducible nitric oxide synthase (iNOS), and HO-1 protein were detected. Hmox1 flox/ floxCre+ /- and Hmox1 -/- (HO-1 M-KO) mice with conditional knockout of HO-1 gene in alveolar macrophages were produced and randomly divided into HO-1 flox/flox Control group, HO-1 flox/flox SW 24 h group, HO-1 M-KO Control group, and HO-1 M-KO SW 24 h Group, with 6 mice in each group. The mouse model of seawater-drowning-induced ALI was established by placing mice in a hollow container and then immersing them in 6 cm deep and (25±2)℃ artificial seawater for 28 s. Samples were taken 24 hours after seawater drowning to carry out alveolar lavage, and then the total cell counts and protein concentrations in bronchoalveolar lavage fluid (BALF), and the pathological changes and the iNOS protein content in lung tissues were observed. Results:Abnormally shaped Raw 264.7 cells increased while the total number of Raw 264.7 cells decreased after seawater stimulation. The apoptosis rates of the control group, SW 8 h group, SW 24 h group, and SW 72 h group were increased to (5.99±0.23)%, (16.71±1.16)%, (41.80±2.50)%, and (77.84±1.59)%, respectively, with statistically significant differences ( P<0.01). The contents of HO-1 protein in the control group, SW 8 h group, SW 24 h group, and SW 72 h group were (1.07±0.06), (1.42±0.01), (2.77±0.22), and (0.99±0.10), respectively, and the contents of HO-1 protein of both SW 8 h group and SW 24 h group increased significantly ( P<0.05). The contents of iNOS protein in the cells of the control group, SW 8 h group, SW 24 h group, and SW 72 h group were (0.94±0.10), (3.44±0.32), (1.52±0.09), and (2.26±0.11), respectively, and the contents of iNOS protein of SW 8 h group, SW 24 h group, and SW 72 h group increased significantly ( P<0.05); compared with the SW 8 h group, the HO-1 protein content increased significantly, while the iNOS protein content decreased in the SW 24 h group significantly ( P<0.01). Lung tissue injury in HO-1 M-KO mice was significantly aggravated after drowning. The cavity of pulmonary alveoli collapsed and shrunk, intra-alveolar hemorrhage occurred, alveolar septum thickened, and inflammatory cell infiltration aggravated. The cell number and protein concentration in BALF significantly increased ( P<0.01), and the iNOS content in lung tissue significantly increased( P<0.01). Conclusion:HO-1 can alleviate the seawater-drowning-induced ALI in mice by inhibiting the M1 macrophage polarization.
