Role and mechanism of nuclear factor erythroid 2-related factor 2 in reducing lung injury in mice with Staphylococcus aureus-induced sepsis
10.3760/cma.j.cn311365-20240729-00223
- VernacularTitle:NRF2对金黄色葡萄球菌感染所致脓毒症小鼠肺损伤的作用研究
- Author:
Hongyi WEI
1
;
Sihao JIN
;
Jiaojiao SUN
;
Chuanxin LIU
;
Rixiang HUANG
;
Zhiqiang WANG
;
Jianjun CHU
Author Information
1. 江南大学附属医院重症医学科，无锡 214122
- Publication Type:Journal Article
- Keywords:
Staphylococcus aureus;
Acute lung injury;
Nuclear factor erythroid 2-related factor 2;
Myeloperoxidase
- From:
Chinese Journal of Infectious Diseases
2024;42(12):750-754
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role and mechanism of nuclear factor erythroid 2-related factor 2 (NRF2) in lung injury in mice with Staphylococcus aureus-induced sepsis. Methods:A sepsis mouse model with Staphylococcus aureus infection was created using wild-type C57BL/6 male mice and NRF2 -/- male mice aged six to eight weeks. The mice were divided into four groups with five in each group. In WT control group and NRF2 -/- control group, the wild type mice and NRF2 -/- mice were intraperitoneally injected with 100 μL phosphate buffered saline (PBS) respectively. In WT model group and NRF2 -/- model group, the wild type mice and NRF2 -/- mice were intraperitoneally injected with 100 μL PBS containing Staphylococcus aureus (3×10 8 colony forming unit (CFU)/mL) respectively. The lung samples were taken under anesthesia six hours after injection, and hematoxylin and eosin staining was performed to observe tissuse lesions. The survival of the mice was evaluated. The protein concentrations and cell counts in the bronchoalveolar lavage fluid (BALF), the mRNA relative expressions of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in lung tissues, and the serum levels of myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) were compared among the four groups. Independent samples t test was used for statistical comparison. Results:After six days of observation, no mice died in WT control group and NRF2 -/- control group, three mice died in WT model group on day 3, and four mice died in NRF2 -/- model group on day 4. The pathological staining showed that macrophage infiltration and alveolar structure damage occurred in the lung tissuse of WT model group, and the damage were more significant in NRF2 -/- model group. The protein concentrations and cell counts in BALF of mice in WT control group were (342±23) μg/mL and (5.78±2.67)×10 5/mL, respectively, those in WT model group were (657±39) μg/mL and (10.78±5.57)×10 5/mL, respectively, those in NRF2 -/- control group were (312±45) μg/mL and (5.67±1.46)×10 5/mL, respectively, and those in NRF2 -/- model group were (957±85) μg/mL and (13.85±3.72)×10 5/mL, respectively. The protein concentrations and cell counts in WT model group were higher than those in WT control group ( t=6.56, P<0.001 and t=8.21, P<0.001, respectively), while lower than NRF2 -/- model group ( t=2.32, P=0.001 and t=3.11, P=0.002, respectively). The differences were all statistically significant. Compared with the WT model group, the mRNA relative expressions of TNF-α (4.345±1.131 vs 12.375±4.534), IL-1β (5.395±2.112 vs 6.865±2.185), IL-6 (2.964±0.945 vs 5.467±1.855) in the lung tissues of NRF2 -/- model group increased, and the serum levels of MPO (2.956±1.211 vs 4.745±1.945) and MDA (4.333±1.652 vs 8.234±3.734) increased, while the level of SOD (17.121±8.183 vs 11.967±8.122) decreased, with statistically differences ( t=1.77, 4.67, 2.99, 7.99, 10.45 and 8.45, respectively, all P<0.05). Conclusions:The absence of NRF2 gene can exacerbate the inflammatory response and oxidative stress in mice with Staphylococcus aureus-induced sepsis, leading to more severe lung tissue damage.
