Role of PKCα-Nrf2-HO-1 signaling pathway in endotoxic shock-induced acute lung injury in rabbits

Abstract

Objective To evaluate the role of protein kinase Cα (PKCα) -nuclear factor E2-related factor 2 (Nrf2) -heme oxygenase-1 (HO-1) signaling pathway on endotoxic shock-induced acute lung injury (ALI) in rabbits. Methods Thirty healthy male New Zealand white rabbits, aged 2 months, weighing 2.0-2.5 kg, were randomly divided into 3 groups (n=10 each) using a random number table: normal control group (group C) ; ALI group (group ALI) ; PKCα inhibitor chelerythrine group (group CHE) . In group CHE, chelerythrine 8 mg/kg (in 0.5 ml of DMSO) was injected intraperitoneally, and 30 min later, LPS 5 mg/kg (in 2 ml of normal saline) was injected via the auricular vein to induce ALI in ALI and CHE groups.The rabbits were then sacrificed at 6 h after injection of LPS or normal saline, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet/dry lung weight ratio (W/D ratio) , and the expression of Nrf2 and HO-1 protein and mRNA. Results Compared with group C, the pathological score and W/D ratio were significantly increased, and the expression of Nrf2 and HO-1 protein and mRNA was up-regulated in ALI and CHE groups.The pathological score and W/D ratio were significantly higher, and the expression of Nrf2 and HO-1 protein and mRNA was lower in group CHE than in group ALI. Conclusion The PKCα-Nrf2-HO-1 signaling pathway is one of the endogenous protective mechanisms underlying endotoxic shock-induced ALI in rabbits. Key words: Protein kinase Cα; NF-E2-related factor 2; Heme oxygenase-1; Shock, septic; Respiratory distress syndrome, adult