Decreased expression of peroxisome proliferator-activated receptor γ endotoxin-induced acute lung injury
Decreased expression of peroxisome proliferator-activated receptor γ endotoxin-induced acute lung injury
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DOI：
10.33549/physiolres.930822
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发表时间：
2006-01-01
影响因子：
2.1
通讯作者：
Shang, Y.
中科院分区：
文献类型：
--
作者：
Liu, D.;Zeng, B. Xiong;Shang, Y.
过氧化物酶体增殖物激活受体-γ（PPAR-gamma）是配体激活转录因子的核激素受体超家族的成员，具有抗炎特性。本研究的目的是研究肺组织中PPAR-gamma的表达，并探讨其在脂多糖（LPS）诱导的急性肺损伤中的功能意义。雄性Wistar大鼠30只，随机分为生理盐水对照组和LPS（6 mg/kg）注射后2 h、4 h、6 h和8h组。在预定的时间点，收集血液样品以测量肿瘤坏死因子（TNF）-α的血浆水平，并取出肺以测定组织病理学变化、湿干重（W/D）比、髓过氧化物酶（MPO）活性和TNF-α水平。同时检测各组肺组织中PPAR-γ的表达和核因子（NF）-κ B p65的活化。LPS注射导致肺组织W/D比值和MPO活性明显升高，肺组织病理学改变不明显。在血浆和肺中也观察到TNF-α水平升高。这些炎症事件与肺中PPAR-gamma蛋白表达减少和NF-κ B活化相关。我们的数据表明，肺中PPAR-gamma蛋白表达的降低可能有助于内毒素血症中持续的肺部炎症和组织损伤。
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors, possesses anti-inflammatory properties. The purpose of the present study was to investigate the profile of PPAR-gamma expression in the lung and to explore its functional significance in lipopolysaccharide (LPS)-induced acute lung injury. Thirty male Wistar rats were randomly assigned to one of the following five groups: saline control group and different LPS groups (2 h, 4 h, 6 h and 8 h after LPS 6 mg/kg i.v.). At predefined time points, blood samples were collected to measure plasma level of tumor necrosis factor (TNF)-alpha and lungs were removed to assay histopathological changes, wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and TNF-alpha level. Expression of PPAR-gamma and activation of nuclear factor (NF)-kappa B p65 in lung tissues were also examined in each group. LPS injection resulted in marked lung damage and elevated levels of W/D ratio and MPO activity in the lung. Increased levels of TNF-alpha were also observed in the plasma and lung. These inflammatory events were associated with reduced expression of PPAR-gamma protein and with activation of NF-kappa B in the lung. Our data suggest that decreased expression of PPAR-gamma protein in lungs may contribute to the ongoing pulmonary inflammation and tissue injury in endotoxemia.