Protective effects of peroxisome proliferation activated receptor-β on hemorrhagic shock-induced acute lung injury in rats

Abstract

Objective To observe the protective effects of peroxisome proliferation activated receptorβ (PPAR-b) on acute lung injury in the wake of hemorrhagic shock in rats in order to illuminate the mechanism.Methods After ALI model of rat was established following hemorrhagic shock,96 SD rats were divided randomly (random number) into 4 groups:group A (sham operation group),group B (ALI group),group C (GSK0660,an antagonist to PPAR-b given prior to exsanguinations for pretreatment) and group D (GW0742,an agonist of PPAR-b given before exsanguinations for pretreatment).Each group was further divided into 1 h,2 h,4 h and 6 h subgroups.Six mice of each subgroup were sacrificed at each interval.Expression of PPAR-β receptor in lung tissues was detected at 1 h,2 h,4 h and 6 hours.Pathological examination and lung wet/dry weight ratio were detected,and lung tissue antioxidant enzyme SOD and 8-iso-PGF2α,the oxidation product of activated GSH-Px were evaluated.Results (①)Antioxidant enzymes SOD and activated GSH-Px were significantly higher in ALI group than those in the sham operation group (P＜0.01).(②Tne antioxidant enzyme SOD and activated GSH-Px in lung tissue in GW0742 group decreased at each interval especially at 2 h and4 h compared with ALI group (P ＜0.01).(③) GW0742 used alone can improvePaO2,W/D ratio of lung tissue of rats,lung pathology integral,and inhibit the activity of SOD and GSH-Px in lung tissue (P ＜ 0.01) and decrease the content of 8-iso-PGF-2α.The antagonist GSK0660 can lessen the above effects (P ＜ 0.01).Conclusions (①)ALI emerged from hemorrhagic shock in rats leading to significantly increased activity of SOD and GSH-Px in lung tissue,suggesting rats subjected to acute oxidative stress.(②)GW0742 can up-regulate the levels of SOD and GSH-Px in lung tissue of rats with ALI.It also decreased the content of 8-iso-PGF2 α,the oxidation products of GSH-Px.(③) It was suggested that GW0742 might inhibit the expression of TNF-α mRNA and level of TNF-a protein,and decreased SOD activity in lung tissue,protecting lung tissue to some degree from ALI and improving PaO2.The mechanism of it may be attributed to preventing NF-κ B activation. Key words: Acute lung injury; Peroxisome proliferator-activated receptor; Oxidative stress; Hemorrhagic shock ; Acute respiratory distress syndrome; Inflammatory response ; Apoptosis ; Mortality