Role of PKCα-Nrf2-HO-1 signaling pathway in endotoxic shock-induced acute lung injury in rabbits / 中华麻醉学杂志

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.