Serotonin-deficient neonatal mice are not protected against the development of experimental bronchopulmonary dysplasia or pulmonary hypertension.
Serotonin-deficient neonatal mice are not protected against the development of experimental bronchopulmonary dysplasia or pulmonary hypertension.
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DOI：
10.14814/phy2.15482
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发表时间：
2022-10
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
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5-羟色胺（5-羟色胺，5-HT）是一种强效肺血管收缩剂，可导致发育中绵羊肺的高肺血管阻力。在实验性肺动脉高压（PH）中，肺组织中色氨酸羟化酶-1（TPH 1）（5-HT合成的限速酶）和血浆5-HT的表达增加。5-HT阻滞剂可增加肺血流量，并防止肺血管重塑和PH新生儿模型中的PH与支气管肺发育不良（BPD）。我们假设新生tph 1基因敲除（KO）小鼠可免受缺氧诱导的肺泡简化、血管密度降低和PH的影响。将新生野生型（WT）和tph 1基因敲除（KO）小鼠暴露于常氧或缺氧2周。常氧WT和KO小鼠表现出相似的肺泡发育、肺血管密度、右心室收缩压（RVSP）和右心大小。在缺氧暴露的WT和KO小鼠中，循环（血浆和血小板）5-HT均降低。与WT小鼠相比，Tph 1 KO小鼠未受到缺氧诱导的肺泡简化、肺血管密度降低或右心室肥大的保护，但显示出对缺氧诱导的RVSP升高的减弱。Tph 1 KO新生小鼠不能抵抗缺氧诱导的肺泡简化、肺血管密度降低或RVH。虽然tph 1的遗传和药理学抑制在成人PH模型中具有保护作用，但我们的研究结果表明，tph 1抑制对伴有BPD的PH新生儿没有益处。5-羟色胺缺乏的新生小鼠不能抵抗缺氧诱导的肺泡简化、肺血管密度降低或RVH。虽然色氨酸羟化酶1（TPH 1）的遗传和药理学抑制在成人肺动脉高压（PH）模型中具有保护作用，但我们的研究结果表明，TPH 1抑制对伴有BPD的PH新生儿没有益处。
Serotonin (5‐hydroxytryptamine, 5‐HT) is a potent pulmonary vasoconstrictor and contributes to high pulmonary vascular resistance in the developing ovine lung. In experimental pulmonary hypertension (PH), pulmonary expression of tryptophan hydroxylase‐1 (TPH1), the rate limiting enzyme in 5‐HT synthesis, and plasma 5‐HT are increased. 5‐HT blockade increases pulmonary blood flow and prevents pulmonary vascular remodeling and PH in neonatal models of PH with bronchopulmonary dysplasia (BPD). We hypothesized that neonatal tph1 knock‐out (KO) mice would be protected from hypoxia‐induced alveolar simplification, decreased vessel density, and PH. Newborn wild‐type (WT) and tph1 KO mice were exposed to normoxia or hypoxia for 2 weeks. Normoxic WT and KO mice exhibited similar alveolar development, pulmonary vascular density, right ventricular systolic pressures (RVSPs), and right heart size. Circulating (plasma and platelet) 5‐HT decreased in both hypoxia‐exposed WT and KO mice. Tph1 KO mice were not protected from hypoxia‐induced alveolar simplification, decreased pulmonary vascular density, or right ventricular hypertrophy, but displayed attenuation to hypoxia‐induced RVSP elevation compared with WT mice. Tph1 KO neonatal mice are not protected against hypoxia‐induced alveolar simplification, reduction in pulmonary vessel density, or RVH. While genetic and pharmacologic inhibition of tph1 has protective effects in adult models of PH, our results suggest that tph1 inhibition would not be beneficial in neonates with PH associated with BPD. Serotonin‐deficient neonatal mice are not protected against hypoxia‐induced alveolar simplification, reduction in pulmonary vessel density, or RVH. While genetic and pharmacologic inhibition of tryptophan hydroxylase 1 (TPH1) has protective effects in adult models of pulmonary hypertension (PH), our results suggest that tph1 inhibition would not be beneficial in neonates with PH associated with BPD.
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影响因子：
4.3
作者：
Chen, Chunyan;Han, Xinyuan;Tian, Hongyan
通讯作者：
Tian, Hongyan
DOI：
10.1124/jpet.116.237933
发表时间：
2017-02-01
影响因子：
3.5
作者：
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通讯作者：
Paralkar, Vishwas
影响因子：
3.4
作者：
Belik, Jaques
通讯作者：
Belik, Jaques
DOI：
10.1152/ajplung.00073.2017
发表时间：
2018-10-01
影响因子：
4.9
作者：
Good, Ryan J.;Hernandez-Lagunas, Laura;Nozik-Grayck, Eva
通讯作者：
Nozik-Grayck, Eva
DOI：
10.1152/ajplung.00215.2017
发表时间：
2018-05-01
影响因子：
4.9
作者：
Delaney, Cassidy;Sherlock, Laurie;Nozik-Grayck, Eva
通讯作者：
Nozik-Grayck, Eva