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. Key words: 1-phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; NF-E2-related factor 2; Endotoxemia; Respiratory distress syndrome, adult
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