The mechanism of imatinib on the regulation of lipopolysaccharide-induced acute lung injury in mice through the Nrf2/HO-1 signaling pathway
10.3760/cma.j.issn.1671-0282.2024.08.006
- VernacularTitle:伊马替尼通过Nrf2/HO-1信号通路调节脂多糖诱导的小鼠急性肺损伤的机制
- Author:
Duanyang LI
1
;
Yaru LIU
;
Zhiqing ZHOU
;
Hong YANG
;
Xiaolong ZONG
;
Zhenyu LI
Author Information
1. 天津医科大学第二医院急诊医学科，天津 300211
- Keywords:
Endotoxemia;
Acute lung injury;
Imatinib;
Heme oxygenase-1;
Oxidative stress;
Lipopolysaccharide;
Nuclear factor-erythroid 2-related factor 2;
nuclear factor
- From:
Chinese Journal of Emergency Medicine
2024;33(8):1104-1109
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods:Sixty SPF male, 8-12 weeks, C57BL/6 mice were randomly (random) divided into 4 groups ( n=15 each): control group (group C), imatinib group (groupⅠ), endotoxemia group (group LPS) and imatinib + endotoxemia group (group I+LPS). The endotoxemia model of acute lung injury was established. After 24 hours, the mice were sacrificed. The pathological changes of lung tissues were evaluated, the lung injury scores were calculated, and the wet/dry ratios of lung tissues were measured. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. Detection kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in lung tissues; The expression levels of phosphorylated nuclear factor-kappa B (p-NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were analyzed by western blotting. Results:Compared with the group C, the wet/dry (W/D) ratio of lungs [(3.47±0.41) vs. (5.58±0.47)], lung injury scores [(1.25±0.89) vs. (10.25±1.75)], and the levels of TNF-α and IL-6 in serum increased in the group LPS ( P<0.05). The levels of SOD, CAT, GSH and GSH/GSSG decreased, the level of MDA increased, and the expression of p-NF-κB, Nrf2 and HO-1 protein up-regulated ( P<0.05). Compared with the LPS group, the W/D ratio of lungs [(5.58±0.47) vs.(4.62±0.38)] and lung injury scores [(10.25±1.75) vs. (7.00±1.31)] in the I+LPS group decreased ( P<0.05), and the levels of TNF-α and IL-6 in the serum decreased ( P<0.05). In lung tissues, the levels of SOD, CAT, GSH and GSH/GSSG increased (all P<0.05), the level of MDA decreased (all P<0.05), the expression of p-NF-κB protein decreased, and the expression of Nrf2 and HO-1 protein increased ( P<0.05). Conclusions:Imatinib improves sepsis-induced acute lung injury in mice, and the mechanism of actions behind may be related to the inhibition of oxidative stress.
