15-deoxy-Δ12,14-prostaglandin J2 ameliorates endotoxin-induced acute lung injury in rats
15-deoxy-Δ12,14-prostaglandin J2 ameliorates endotoxin-induced acute lung injury in rats
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DOI：
10.3760/cma.j.issn.0366-6999.20131079
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发表时间：
2014-03-05
影响因子：
6.1
通讯作者：
Liang Juan
中科院分区：
文献类型：
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作者：
Liu Dong;Geng Zhilong;Liang Juan
研究背景中性粒细胞聚集和活化导致的肺内炎症环境是急性肺损伤（ALI）发病机制的关键。15-脱氧-δ（12，14）-前列腺素J（2）（15 d-PGJ（2））是环氧合酶-2途径的终末产物之一，是过氧化物酶体增殖物激活受体γ（PPAR-gamma）的内源性配体，具有多种生理特性。越来越多的证据表明15 d-PGJ（2）具有抗炎、抗增殖、细胞保护和促消退作用。方法雄性Wistar大鼠24只，随机分为假手术+溶媒组、假手术+15 d-PGJ（2）组、LPS+溶媒组和LPS+15 d-PGJ（2）组，每组6只。给大鼠静脉注射脂多糖（LPS，6 mg/kg）或生理盐水，并在注射LPS前30分钟用15 d-PGJ（2）（0.3 mg/kg）或其载体（二甲基亚砜）预处理。LPS注射后4小时，在肺组织中测定组织学改变、湿/干重（W/D）比和髓过氧化物酶（MPO）活性以及肿瘤坏死因子（TNF）-α和嘌呤诱导的中性粒细胞趋化因子-1（CINC-1）水平。结果15 d-PGJ（2）预处理可明显减轻LPS诱导的肺损伤，降低肺W/D比值、MPO活性、TNF-α、CINC-1和ICAM-1表达。结论15 d-PGJ（2）对内毒素诱导的急性肺损伤具有保护作用，其机制可能是通过抑制NF-κ B活化，降低内毒素血症时炎性蛋白水平。
Background A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury (ALI). 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), one of the terminal products of the cyclooxygenase-2 pathway, is known to be the endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR-gamma) with multiple physiological properties. Growing evidence indicates that 15d-PGJ(2) has anti-inflammatory, anti-proliferative, cytoprotective and pro-resolving effects. We investigated whether 15d-PGJ(2) has a protective effect against endotoxin-induced acute lung injury in rats.Methods Twenty-four male Wistar rats were randomly assigned into four groups (n=6 per group): sham+vehicle group, sham+15d-PGJ(2) group, LPS+vehicle group, and LPS+15d-PGJ(2) group. The rats were given either lipopolysaccharide (LPS, 6 mg/kg intravenously) or saline, and pretreated with 15d-PGJ(2) (0.3 mg/kg intravenously) or its vehicle (dimethyl sulphoxide) 30 minutes before LPS. Histological alterations, wet/dry weight (W/D) ratio and myeloperoxidase (MPO) activity as well as tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels were determined in lung tissues four hours after LPS injection. Immunohistochemical analysis for intercellular adhesion molecule-1 (ICAM-1) expression and Western blotting analysis for nuclear factor (NF)-kappa B p65 translocation and I kappa B alpha protein levels were also studied.Results 15d-PGJ(2) pretreatment significantly attenuated LPS-induced lung injury, and reduced the increased W/D ratio, MPO activity, TNF-alpha, CINC-1 levels, and ICAM-1 expression in the lung. 15d-PGJ(2) also suppressed the nuclear NF-kappa B p65 translocation and increased cytosolic I kappa B alpha levels.Conclusions 15d-PGJ(2) protects against endotoxin-induced acute lung injury, most likely through the reduction of inflammatory protein levels during endotoxemia subsequent to the inhibition of NF-kappa B activation.