首页> 外文期刊>American Journal of Physiology >Vascular changes after intra-amniotic endotoxin in preterm lamb lungs.
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Vascular changes after intra-amniotic endotoxin in preterm lamb lungs.

机译:羊膜内羊水中羊膜内毒素后的血管变化。

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Chorioamnionitis is associated with preterm delivery and bronchopulmonary dysplasia (BPD), characterized by impaired alveolar and pulmonary vascular development and vascular dysfunction. To study the vascular effects in a model of chorioamnionitis, preterm lambs were exposed to 20 mg of intra-amniotic endotoxin or saline for 1, 2, 4, or 7 days and delivered at 122 days gestational age (term = 150 days). This intra-amniotic endotoxin dose was previously shown to induce lung maturation. The effect of intra-amniotic endotoxin on expression of endothelial proteins was evaluated. Muscularization of the media and collagen deposition in adventitia of small pulmonary arteries was used to assess vascular remodeling. Compared with controls, bronchoalveolar lavage fluid protein content was increased 2 days after intra-amniotic endotoxin exposure. Vascular endothelial growth factor (VEGF) 165 isoform mRNA decreased 2-4 days after intra-amniotic endotoxin. VEGF, VEGF receptor-2, endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, and Tie-2 protein expression in the lung coordinately decreased 1-7 days after intra-amniotic endotoxin. Intra-amniotic endotoxin appeared to selectively decrease eNOS expression in small pulmonary vessels compared with large vessels. Medial smooth muscle hypertrophy and increased adventitial fibrosis were observed 4 and 7 days after intra-amniotic endotoxin. These results demonstrate that, in the preterm lamb lung, antenatal inflammation inhibits endothelial cell protein expression followed by vascular remodeling changes in small pulmonary arteries. Exposure to antenatal inflammation may cause vascular remodeling and contribute to the development of BPD.
机译:绒毛膜羊膜炎与早产和支气管肺发育不良(BPD)有关,其特征是肺泡和肺血管发育受损和血管功能障碍。为了研究脉络膜羊膜炎模型中的血管作用,将早产羔羊暴露于20 mg羊膜内毒素或生理盐水中1、2、4或7天,并在其胎龄为122天时(足月= 150天)分娩。羊水内毒素的剂量先前已显示出可诱导肺成熟。评估了羊膜内毒素对内皮蛋白表达的影响。小肺动脉外膜中介质的肌肉化和胶原沉积被用来评估血管重塑。与对照组相比,羊膜内毒素暴露2天后支气管肺泡灌洗液蛋白质含量增加。羊膜内毒素后2-4天,血管内皮生长因子(VEGF)165亚型mRNA下降。羊膜内内毒素后1-7天,肺中的VEGF,VEGF受体2,内皮型一氧化氮合酶(eNOS),血小板内皮细胞粘附分子1和Tie-2蛋白表达协调下降。与大血管相比,羊膜内毒素似乎选择性降低了小肺血管中eNOS的表达。羊膜内内毒素后4天和7天观察到内侧平滑肌肥大和外膜纤维化增加。这些结果表明,在早产羔羊肺中,产前炎症抑制内皮细胞蛋白表达,继而抑制小肺动脉中的血管重塑变化。暴露于产前炎症可能会导致血管重塑,并导致BPD的发展。

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