中文摘要：

目的探讨激活过氧化物酶增殖物激活受体-α对急性肺损伤大鼠肺组织TNF-α mRNA表达的抑制作用及对其自身表达的影响,旨在揭示PPAR-α在急性肺损伤中的保护作用及机制。方法将120只大鼠随机分为对照组（ND组）、脂多糖（LPS）致伤组（LD组）、WY14643处理组（LW组）、MK886处理组（LM组）、WY14643＋MK886处理组（LWM组）。用LPS 5mg/kg静脉注射复制大鼠ALI模型。静脉注射WY14643 3mg/kg（LW组）或MK886 3mg/kg（LM组）或顺序注入此两种干预药物（LWM组,间隔30min）,30min后静脉注射LPS（注射LPS后开始计时）。分别在1,2,4h及8h时处死大鼠,测定用药前后各时相点大鼠肺组织湿/干重比（W/D）及肺组织病理变化;采用逆转录聚合酶链反应（RT-PCR）检测各时相点肺组织中PPAR-α mRNA、肿瘤坏死因子-α（TNF-α）mRNA的表达。结果LD组、LM组、LWM组肺组织病理积分及干湿重比值均较ND组明显升高（P〈0.05）,LW组较ND组、LD组明显降低（P〈0.05）,LM组较LD组明显降低（P〈0.05）,LWM组较LD组无统计学意义（P〉0.05）;正常肺组织可表达PPAR-αmNRA,LD组PPAR-α mRNA在1h开始下降,2h降至谷底,持续至实验结束,TNF-α mNRA于2h升至高峰,此后下降;LW组PPAR-α mRNA较LD组显著升高LPS致伤（P〈0.05）,2h升至高峰,TNF-α mRNA于2h时降低较明显;LM组肺组织PPAR-α mRNA较LD组显著降低（P〈0.05）,在4h降至谷底,持续至实验结束,而TNF-α mRNA较LD组显著升高（P〈0.05）;LWM组显示WY14643的作用被MK886所抑制。结论LPS引起急性肺损伤大鼠肺组织PPAR-α mRNA表达下降,TNF-α mRNA,WY14643使上述改变减轻,MK886引起TNF-αmR-NA进一步升高,且MK886对抗WY14643的作用。其机制可能是过氧化物酶增殖体激活受体-α激活后抑制了TNF-α的表达,从而对急性肺损伤的炎症反应进行有效的调控。

英文摘要：

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 mrs 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 rots were killed at 1h,2h,4h,8h after LPS challenge. Lung tissue wet/dry weight ratio, lung histopathologieal change were observed, expression of PPAR-α and TNF-α mRNA were explored by RT-PCR. Results lung W/D ratio and histopathology integral m LD group,LM group and LWM group rised compare with control group（ P 〈 0.05）, which in LW group decreased compare with control group（ P 〈 0.05 ） and LD group（ P 〈 0.05 ）, and those in LWM group had no distinction compare with LD group（ P 〉 0.05）.Lung tissue of normal rots expressed PPAR-α. PPAR-α mRNA expression in LD group and LWM group decreased since lh 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（ P 〈 0.05）. PPAR-α m/LNA 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 P