15-脱氧- 12,14-前列腺素j2(15dpgj2) 对内毒素 - 第三军医大学学报.doc

15-脱氧-△12,14-前列腺素J2对内毒素静脉推注致急性肺损伤型的肺保护作用 吕 锐，吴 艳，申江华，曾子洋，易 斌，鲁开智 基金项目：国家自然科学基金81170414） 作者单位：400038 重庆市，第三军医大学附属西南医院麻醉科 通信作者：鲁开智Email:lukaizhi2010@163.com [摘要] 目的 探讨脂多糖(lipopolysaccharide, LPS)推注致大鼠急性肺损伤时15-脱氧-△12,14-前列腺素J2(15-deoxy-Δ12,14-prostaglandin J2, 15d-PGJ2)对肺组织的炎症因子cp65表达的影响。方法 将40只SD大鼠按随机数字表法随机分为4组，每组10只，分别为对照组、15d-PGJ2组、LPS组和LPS+ 15d-PGJ2组[1,2]。四组尾静脉分别注射二甲基亚砜二甲基亚砜 LPS组和LPS+15d-PGJ2组均注射LPS（6mg/kg）。4小时后检测肺动脉血气，测量肺湿/干质量比（W/D），及肺组织中TNF-α，IL-8，CINC-1Western blot检测NF-κB p65和IκBα蛋白的表达。结果 LPS组与对照组比较肺W/D，TNF-α，IL-8，CINC-1水平和NF-κB p65蛋白均显著升高，IκBα蛋白表达显著降低(P0.05)；与LPS组比较，15d-PGJ2+LPS组肺W/D，TNF-α，IL-8，CINC-1水平和NF-κB p65显著降低，IκBα蛋白表达显著升高(P0.05)。15d-PGJ2预处理能明显减轻LPS所致的急性肺损伤程度，降低肺W/D，减少TNF-α，IL-8，CINC-1的表达，抑制NF-κB p65，提高IκBα蛋白表达。结论 15d-PGJ2通过抑制NF-κB p65信号通路，减少炎症因子的释放对内毒素静脉推注致急性肺损伤发挥保护作用。 [关键词] 急性肺损伤；15-脱氧-△12,14-前列腺素J2；TNF-α；IL-8；CINC-1；NF-κВ p65；IκBα；Protective effects of 15d-PGJ2 against endotoxin-induced acute lung injury in rats and its mechanism Lv Rui,Wu Yan,Shen Jianghua,Zen Zhiyang,Yi Bin, Lu Kaizhi（Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China ） [Abstract] Objective To explore the effects of 15dPGJ2 on the expressions of TNF-α，IL-8，CINC-1， NF-κB p65IκBα in rat model of acute lung injury induced by lipopolysaccharide(LPS). Methods Twenty?four rats were random divided into four groups (n=6 per group):control group,LPS group,15d-PGJ2 group and LPS+15d-PGJ2 treatment group．To copy the rat model of acute lung injury，LPS(6 mg/kg)was injected into the tail vein．The SD rats were given either lipopolysaccharide (LPS, 6 mg/kg) or saline, and pretreated with (0.3 mg/kg intravenously) or dimethyl sulphoxide 30 minutes before LPS. four hours after LPS or dimethyl sulphoxide injection The expressions of TNF-α,IL-8,CINC-1 were detected by elisa. The expressions of NF-κB p65 and IκBα protein were evaluated by western blot analysis.Results Compared with control group，expression of TNF-α,IL-8