The role of peroxisome proliferation activated receptor-α activated ligands in acute lung injury induced by lipopolysaccharide in rats

Objective To investigate the role and possible mechanism of a peroxisome proliferator-activated receptors(PPARα) ligand,WY14643,in acute lung injury rat model induced by lipopolysaccharide.Methods 104 male Wistar rats were divided randomly into four groups,ie,control group,acute lung injury group,WY14643 1 mg group and WY14643 3 mg group.Wistar rats were challenged with lipopolysaccharide((5 mg/kg)) before intratracheal administration with WY14643(1 mg/kg and 3 mg/kg).All rats were killed at 1 h,2 h,4 h,and 8 h after LPS challenge.The ratio of lung wet weight to dry weight and pulmonary morphologic changes were measured while the expression of tumor necrosis factor-α(TNF-α) mRNA in lung was detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR)and the level of TNF-α in supernatant of rats lung homogenate was measured by ELISA.Results WY14643 1 mg and WY14643 3 mg treatment at 2 h and 4 h alleviated the pathological changes while the ratio of wet weight to dry weight was significantly lower compared to those in ALI group(P0.01).TNF-α mRNA expression and TNF-α concentration in supernatant of lung homogenate at 2 h,4 h,and 8 h in WY14643 1 mg group,at 1 h,2 h,4 h, and 8 h in WY14643 3 mg group were significantly lower than those in ALI group(P0.05,P0.01).Treatment with WY14643 at a dose of 1 mg/kg or 3 mg/kg ameliorated the neutrophilic lung inflammation and pulmonary edema induced by lipopolysaccharide.Conclusions Our data suggest WY14643 could inhibit the expression of TNF-α mRNA and nuclear translocalization of nuclear factor-κB and AP-1 and ameliorate the neutrophilic lung inflammation and pulmonary edema induced by lipopolysaccharide.WY14643 may be a promising option for therapy of acute lung injury.