Epidermal growth factor receptor inhibition with Gefitinib does not alter lung responses to mechanical ventilation in fetal, preterm lambs.
Epidermal growth factor receptor inhibition with Gefitinib does not alter lung responses to mechanical ventilation in fetal, preterm lambs.
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DOI：
10.1371/journal.pone.0200713
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hillman NH
中科院分区：
文献类型：
--
作者：
Kothe TB;Royse E;Kemp MW;Usuda H;Saito M;Musk GC;Jobe AH;Hillman NH
表皮生长因子受体（EGFR）是重要的气道分支和肺成熟。早产羔羊的机械通气导致肺中EGFR和EGFR配体mRNA的增加。EGFR信号异常可能有助于支气管肺发育不良的发展。抑制EGFR信号传导将减少早产胎羊机械通气引起的气道上皮细胞增殖和肺部炎症。在胎龄123 ± 1天暴露胎仔头部和胸部后，胎盘循环完整，（n = 4 - 6/组）随机分配至：1）吉非替尼15 mg IV和1 mg气管内或2）盐水IV和IT。羔羊进一步分配至15分钟的以下任一组：a）有创机械通气（MV）或B）持续气道正压通气（CPAP）5 cm H2O。在15分钟干预后，将动物返回子宫，并在i）6或ii）24小时后在子宫内分娩。MV引起肺损伤和炎症，增加肺细胞因子和EGFR配体的mRNA，引起气道上皮细胞增殖，并降低气道上皮磷酸化ERK 1/2。吉非替尼对MV的反应无变化。吉非替尼改变了CPAP和MV动物肺和肝中EGFR mRNA的表达。吉非替尼在6小时降低肝脏SAA 3 mRNA对MV的反应。接受吉非替尼或生理盐水的CPAP动物之间的肺损伤或炎症标志物没有差异。EGFR通路的抑制并没有改变早产绵羊的急性肺部炎症或机械通气损伤。
Epidermal growth factor receptor (EGFR) is important for airway branching and lung maturation. Mechanical ventilation of preterm lambs causes increases in EGFR and EGFR ligand mRNA in the lung. Abnormal EGFR signaling may contribute to the development of bronchopulmonary dysplasia. Inhibition of EGFR signaling will decrease airway epithelial cell proliferation and lung inflammation caused by mechanical ventilation in preterm, fetal sheep. Following exposure of the fetal head and chest at 123±1 day gestational age and with placental circulation intact, fetal lambs (n = 4-6/group) were randomized to either: 1) Gefitinib 15 mg IV and 1 mg intra-tracheal or 2) saline IV and IT. Lambs were further assigned to 15 minutes of either: a) Injurious mechanical ventilation (MV) or b) Continuous positive airway pressure (CPAP) 5 cmH2O. After the 15 minute intervention, the animals were returned to the uterus and delivered after i) 6 or ii) 24 hours in utero. MV caused lung injury and inflammation, increased lung mRNA for cytokines and EGFR ligands, caused airway epithelial cell proliferation, and decreased airway epithelial phosphorylated ERK1/2. Responses to MV were unchanged by Gefitinib. Gefitinib altered expression of EGFR mRNA in the lung and liver of both CPAP and MV animals. Gefitinib decreased the liver SAA3 mRNA response to MV at 6 hours. There were no differences in markers of lung injury or inflammation between CPAP animals receiving Gefitinib or saline. Inhibition of the EGFR pathway did not alter acute lung inflammation or injury from mechanical ventilation in preterm sheep.
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DOI：
10.1152/ajplung.00294.2010
发表时间：
2011-02-01
影响因子：
4.9
作者：
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发表时间：
2008-06-01
影响因子：
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作者：
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通讯作者：
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作者：
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