【摘要】 目的探讨新型抗炎药物吡菲尼酮(PFD)对大鼠油酸(OA)性急性呼吸窘迫综合征(ARDS)的氧化-抗氧化的影响。方法129只SD大鼠,分为正常对照组、油酸组和3个不同剂量的PFD干预组(20、40、80mg/kg灌胃);根据取材观察时间每组又分为0.5、1、2、6、24h5个亚组。动态观察PFD对氧自由基生成酶[如NADPH氧化酶、黄嘌呤氧化酶(XO)和髓过氧化物酶(MPO)等]及清除氧自由基物质如谷胱甘肽过氧化物酶(GSH-Px)活力和总抗氧化能力(TAC)的作用。结果PFD可降低OA性ARDS大鼠肺组织的自由基含量和氧自由基生成酶(如NADPH氧化酶、XO和MPO等)活力;同时可增强肺组织中GSH-Px活力和TAC。结论PFD对OA性ARDS具有早期干预作用,主要是抑制产生自由基的酶类尤其是NADPH氧化酶活力,从而达到避免自由基直接损伤肺组织的目的。更多还原

【Abstract】 Objective To provide evidences for the potential role of pirfenidone(PFD),an antifibrotic compound with anti-inflammatory effects,on oxidation and antioxidation in acute lung injury induced by oleic acid(OA)in rats.Methods SD rats were randomized into 5 groups(5 rats per group):①the control group received only 0.4% methylcellulose vehicle solution;②ARDS group administered OA(0.15 ml/kg,iv)and 0.4% methylcellulose vehicle solution;③ 3 PFD intervened groups(20,40 and 80 mg/kg,p.o,respectively).The animal model of ARDS was verify by blood gas analysis and pathological examination of lung.Myeloperoxidase(MPO)activity,xantihne oxidase(XO)activity,the important component of nictinamide adeninedinucleotide phosphate oxidase(NADPH oxidase)-P47 expression,glutathione peroxidase(GSH-Px)activity,total antioxidation capability(TAC)were examined at 0.5,1,2,6 and 24 hours after OA challenge.Results PFD could reduce the activities of reactive oxygen species(ROS)generating enzymes including NADPH oxidase,XO and MPO.PFD enhanced the removal of ROS by GSH-Px and TAC.Conclusion PFD mainly decreases the production of ROS in the lung by increasing antioxidant capacity,especially by decreasing NADPH oxidase which avoids the direct lung damage by ROS in OA induced ALI/ARDS.更多还原