Role of PI3K/Akt/Nrf2 signaling pathway in endotoxic shock-induced acute lung injury in rabbits
10.3760/cma.j.issn.0254-1416.2015.10.023
- VernacularTitle:PI3K/Akt/Nrf2信号通路在兔内毒素休克诱发急性肺损伤中的作用
- Author:
Jing ZHANG
;
Jia SHI
;
Jianbo YU
;
Lirong GONG
;
Lili WU
;
Yan XU
- Publication Type:Journal Article
- Keywords:
1-phosphatidylinositol 3-kinase;
Protein-serine-threonine kinases;
NF-E2-related factor 2;
Endotoxemia;
Respiratory distress syndrome,adult
- From:
Chinese Journal of Anesthesiology
2015;35(10):1257-1260
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor E2-related factor 2 (Nrf2) signaling pathway in endotoxic shock-induced acute lung injury (ALI) in rabbits.Methods Thirty healthy male New Zealand white rabbits, aged 2 months, weighing 1.5-2.0 kg, were randomly divided into 3 groups (n =10 each) using a random number table: control group (group C), ALI group, and wortmannin group (group W).In group W, wortmannin 0.6 mg/kg (in 0.08 ml/kg dimethyl sulfoxide) was injected via the auricular vein, while the equal volume of normal saline was given in C and ALI groups.And 30 min later, lipopolysaccharide (LPS) 5 mg/kg (in 2 ml of normal saline) was injected via the auricular vein in ALI and W groups, while the equal volume of normal saline was given in group C.The rabbits were sacrificed at 6 h after LPS or normal saline injection.The lung was immediately removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio), expression of phosphorylated Akt (p-Akt) , Nrf2 and heme oxygenase-1 (HO-1) (by Western blot), and expression of Nrf2 and HO-1 mRNA (using fluorescent quantitative real-time reverse transcriptase-polymerase chain reaction).The pathological changes of the lung were scored.Results Compared with group C, the lung injury scores and W/D ratio were significantly increased, and the expression of p-Akt, Nrf2 protein and mRNA, and HO-1 protein and mRNA was up-regulated in ALI and W groups (P＜0.05).Compared with group ALI, the lung injury scores and W/D ratio were significantly increased,and the expression of p-Akt, Nrf2 protein and mRNA, and HO-1 protein and mRNA was up-regulated in group W (P＜0.05).Conclusion Activation of PI3K/Akt/Nrf2 pathway is the regulatory mechanism of the body adapting to the development of endotoxic shock-induced ALI in rabbits.
