Relationship between Nrf2-ARE pathway and acute lung injury induced by endotoxic shock in rabbits

Objective To evaluate the relationship between erythroid 2-related factor （Nrf2 ）-antioxidant response element （ARE） pathway and acute lung injury （ALI） induced by endotoxic shock 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） ,group ALI and all-trans retinoic acid group （group ATRA ） .In group ATRA ,all-trans retinoic acid 6 mg/kg （in filter sterilized vegetable oil 1.2 ml） was injected intraperitoneally once a day for 2 days .ALI was induced by lipopolysaccharide 5 mg/kg （in normal saline 2 ml ） injected via the auricular vein at 10 h after the last injection of ATRA in ALI and ATRA groups .The equal volume of normal saline was injected instead in group C .The rabbits were sacrificed at 6 h after lipopolysaccharide or normal saline administration .The pulmonary specimens were removed for determination of wet/dry lung weight ratio （W/D ratio ） and expression of Nrf2 mRNA and nuclear protein ,and HO-1 mRNA and protein in lung tissues .The pathological changes of lungs were scored .Results Compared with group C ,the pathological score and W/D ratio were significantly increased , and the expression of Nrf2 mRNA and nuclear protein ,and HO-1 mRNA and protein was up-regulated in ALI and ATRA groups （ P 0.05 ） .Conclusion Activation of Nrf2-ARE pathway is the regulatory mechanism of the body adapting to the ALI induced by endotoxic shock in rabbits . Key words: NF-E2-related factor 2; Response elements; Shock,septic; Respiratory distress syndrome,adult