Role of Nrf2/HO-1 signaling pathway in attenuation of endotoxin-induced acute lung injury by hydromorphone and relationship with Golgi apparatus stress in mice
10.3760/cma.j.cn131073-20241013-00514
- VernacularTitle:Nrf2/HO-1信号通路在氢吗啡酮减轻小鼠内毒素性ALI中的作用：与高尔基体应激的关系
- Author:
Shaona LI
1
;
Yexiang XU
;
Cuicui LIU
;
Wei FENG
;
Yanting WANG
Author Information
1. 青岛大学附属医院麻醉科，青岛 266000
- Publication Type:Journal Article
- Keywords:
NF-E2-related factor 2;
Heme oxygenase-1;
Hydromorphone;
Endotoxins;
Acute lung injury;
Golgi apparatus;
Stress
- From:
Chinese Journal of Anesthesiology
2025;45(5):597-602
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.
