PPARγ受体激动剂抑制急性肺损伤大鼠肺脏粘附分子和趋化因子的表达

目的：探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂-罗格列酮(ROSI)对急性肺损伤大鼠肺脏细胞间粘附分子-1(ICAM-1)和中性粒细胞趋化因子(CINC)-1表达的影响。方法：雄性Wistar大鼠36只，随机分为对照组、ROSI组、GW9662 (PPARγ拮抗剂)组、脂多糖(LPS，6 mg/kg iv) 组、ROSI-LPS组(ROSI 0.3 mg iv+LPS)和GW9662-ROSI-LPS组(ROSI给药前20 min iv 0.3 mg/kg GW9662)。注射LPS后4 h测定肺组织湿/干重比（W/D）、髓过氧化物酶(MPO)活性、丙二醛（MDA）和CINC-1含量，免疫组化法检测肺组织ICAM-1蛋白表达。结果：ROSI预处理能显著抑制LPS所致肺组织MPO活性和MDA含量升高，减轻肺水肿，并降低CINC-1和ICAM-1的蛋白表达(P<0.01)。上述效应可被PPARγ拮抗剂逆转。结论：ROSI预处理能减轻LPS诱导的肺损伤，其机制可能通过激活PPARγ，从而抑制肺组织ICAM-1和CINC-1的表达。

Peroxisome proliferator - activated receptor γ agonist attenuates ICAM - 1 and CINC -1 expression in lungs of rats with acute lung injury

AIM：To investigate the effects of rosiglitazone (ROSI),an agonist of peroxisome proliferator-activated receptor γ (PPARγ),on the lung expression of intercellular adhesion molecule-1 (ICAM-1) and cytokine-induced neutrophil chemoattractant (CINC) in rats with acute lung injury.METHODS：Thirty-six male Wistar rats were randomly divided into six groups：control group,ROSI group,GW9662 (a PPARγ antagonist) group,lipopolysaccharide (LPS,6 mg/kg,iv) group,ROSI-LPS group (0.3 mg/kg ROSI iv 30 min prior to LPS) and GW9662-ROSI-LPS group (0.3 mg/kg GW9662,iv,20 min before ROSI).Four hours after LPS injection,wet/dry weight (W/D) ratio,myeloperoxidase (MPO) activity,malondialdehyde (MDA) and CINC-1 concentrations were assayed in the lung tissues.Immunohistochemical analysis of ICAM-1 expression was also studied.RESULTS：Pretreatment with ROSI significantly attenuated LPS-induced increases in W/D ratio,MPO activity,MDA and CINC-1 concentrations as well as ICAM-1 expression in the lung tissues.The specific PPARγ antagonist GW9662 antagonized the effects of ROSI.CONCLUSION：Pretreatment with ROSI reduces LPS-induced lung injury in rats.The mechanism involves inhibition of the lung expression of ICAM-1 and CINC-1 by the activation of PPARγ.