The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury.
The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury.
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DOI：
10.1186/cc9301
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Rosenberger P
中科院分区：
文献类型：
--
作者：
Mutz C;Mirakaj V;Vagts DA;Westermann P;Waibler K;König K;Iber T;Nöldge-Schomburg G;Rosenberger P
急性肺损伤（acute lung injury，ALI）是一种肺源性或肺外源性炎症性疾病。我们先前已经证明netrin-1抑制小鼠ALI，并且为了将这一发现推进到未来的临床实践中，我们评估了netrin-1是否会减少猪ALI期间的肺泡炎症。这是一项在猪中进行的对照体内实验研究。采用脂多糖（LPS）50 μg/kg持续2小时诱导ALI模型。在此之后，我们将动物暴露于载体、静脉内netrin-1（netrin-1 i. v.）或吸入netrin-1（netrin-1 inh.）。在基线和治疗后6 h采集血清和支气管肺泡灌洗（BAL），测定肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、白细胞介素-6和白细胞介素-8水平。在BAL中测定髓过氧化物酶活性（MPO）和蛋白水平，并获得组织样本进行组织学评价。最后，对动物进行螺旋CT扫描。LPS输注后，动物发生急性肺损伤。静脉注射netrin-1组血清TNF-α和IL-6水平显著降低。BAL显示netrin-1治疗后6小时细胞因子水平显著降低（TNF-α：溶媒633 ± 172 pg/ml，netrin-1静脉注射84 ± 5 pg/ml，netrin-1 inh. 168 ± 74 pg/ml，P均< 0.05。MPO活性和蛋白质含量显着降低BAL样本netrin-1治疗的动物。组织切片证实netrin-1治疗的动物中炎症变化减少。计算机断层扫描证实两个netrin-1治疗组的肺损伤减少。我们的结论是，治疗与内源性抗炎蛋白netrin-1减少肺部炎症在急性肺损伤的初始阶段，并应追求作为未来的治疗选择。
Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI. This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 μg/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT. Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-α and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-α: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups. We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option.
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影响因子：
4.4
作者：
Reutershan, Jorg;Cagnina, Rebecca E.;Ley, Klaus
通讯作者：
Ley, Klaus
影响因子：
158.5
作者：
Amato, MBP;Barbas, CSV;Carvalho, CRR
通讯作者：
Carvalho, CRR
影响因子：
4.8
作者：
Kong, Tianqing;Westerman, Karen A.;Colgan, Sean P.
通讯作者：
Colgan, Sean P.
DOI：
10.1186/cc2881
发表时间：
2004-12
期刊：
Critical care (London, England)
影响因子：
--
作者：
Reutershan J;Ley K
通讯作者：
Ley K
影响因子：
8.8
作者：
Parsons, PE;Eisner, MD;Wheeler, AP
通讯作者：
Wheeler, AP