Effects of activing peroxisome proliferation activated receptor-α on acute lung injury induced by lipopolysaccharide in rats and mechanisms.

Objective To investigate inhibitory action of TNF-αmRNA expression by activing peroxisome proliferation activated receptor-α(PPAR-α)on acute lung injury induced by lipopolysaccharide in rats and effects on expression of PPAR-α,we want to expose the role and mechanisms of PPAR-α in acute lung injury.Methods 120 male Wistar rats were divided randomly into five groups,ie,control group,acute lung injury group,WY14643 group,MK886 group,WY14643+MK886 group.The latter four groups Wistar rats were all injected in LPS(5mg/kg)by vein,which would be provided at the end of 30 minute after vein administration with WY14643 and(or) MK886 especially in LW group、LM group and LWM group.All rats were killed at 1h,2h,4h,8h after LPS challenge.Lung tissue wet/dry weight ratio,lung histopathological change were observed,expression of PPAR-α and TNF-α mRNA were explored by RT-PCR.Results lung W/D ratio and histopathology integral in LD group、LM group and LWM group rised compare with control group(P0.05),which in LW group decreased compare with control group(P0.05)and LD group(P0.05),and those in LWM group had no distinction compare with LD group(P0.05).Lung tissue of normal rats expressed PPAR-α.PPAR-α mRNA expression in LD group and LWM group decreased since 1h post-injury,and declined to valley at 2h post-injury(at 4h post-injury in LW group)and maintained a low level until to end of observation period,but TNF-α mRNA expression increased markedly at 2h(P0.05).PPAR-α mRNA expression in LW group increased markedly compare with LD group and to peak at 2h post-injury,TNF-α decreased significantly at 2h.In LWM group effects of WY14643 were repressed by MK886.Conclusion LPS caused decrease of PPAR-α mRNA and increase of TNF-α mRNA expression in acute lung injury.WY14643 maked change above lessen,but MK886 maked it aggravated.The mechanisms of regulation to inflammation on acute lung injury may be associated with activation of PPAR-α and repression of TNF-α.