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正常和患肺动脉高压新生犊牛的肺内皮细胞增殖

Lung endothelial cell proliferation in normal and pulmonary hypertensive neonatal calves.

作者信息

Stiebellehner L, Belknap J K, Ensley B, Tucker A, Orton E C, Reeves J T, Stenmark K R

机构信息

Division of Pediatric Critical Care, University of Colorado Health Sciences Center, Denver 80262, USA.

出版信息

Am J Physiol. 1998 Sep;275(3):L593-600. doi: 10.1152/ajplung.1998.275.3.L593.

DOI:10.1152/ajplung.1998.275.3.L593
PMID:9728055
Abstract

Tremendous changes in pressure and flow occur in the pulmonary and systemic circulations after birth, and these hemodynamic changes should markedly affect endothelial cell replication. However, in vivo endothelial replication rates in the neonatal period have not been reported. To label replicating endothelial cells, we administered the thymidine analog bromodeoxyuridine to calves approximately 1, 4, 7, 10, and 14 days old before they were killed. Because we expected the ratio of replicating to nonreplicating cells to vary with vascular segment, we examined the main pulmonary artery, a large elastic artery, three sizes of intrapulmonary arteries, the aorta, and the carotid artery. In normoxia for arteries < 1,500 micron, approximately 27% of the endothelial cells were labeled on day 1 but only approximately 2% on day 14. In the main pulmonary artery, only approximately 4% of the endothelial cells were labeled on day 1 and approximately 2% on day 14. In contrast, in the aorta, approximately 12% of the endothelial cells were labeled on day 1 and approximately 2% on day 14. In chronically hypoxic animals, only approximately 14% of the endothelial cells were labeled on day 1 in small lung arteries and approximately 8% were still labeled on day 14. We conclude that the postnatal circulatory adaptation to extrauterine life includes significant changes in endothelial cell proliferation that vary dramatically with time and vascular location and that these changes are altered in chronic hypoxia.

摘要

出生后,肺循环和体循环中的压力和血流会发生巨大变化,这些血流动力学变化应会显著影响内皮细胞的复制。然而,新生儿期体内内皮细胞的复制率尚未见报道。为标记正在复制的内皮细胞,我们在处死前分别给约1日龄、4日龄、7日龄、10日龄和14日龄的小牛注射胸腺嘧啶类似物溴脱氧尿苷。由于我们预期复制细胞与非复制细胞的比例会因血管段而异,因此我们检查了主肺动脉(一条大的弹性动脉)、三种不同大小的肺内动脉、主动脉和颈动脉。在正常氧合状态下,对于直径小于1500微米的动脉,约27%的内皮细胞在第1天被标记,但在第14天仅约2%被标记。在主肺动脉中,第1天仅约4%的内皮细胞被标记,第14天约2%被标记。相比之下,在主动脉中,第1天约12%的内皮细胞被标记,第14天约2%被标记。在慢性缺氧动物中,小肺动脉中第1天仅约14%的内皮细胞被标记,第14天仍有约8%被标记。我们得出结论,出生后循环系统对宫外生活的适应包括内皮细胞增殖的显著变化,这些变化随时间和血管位置而显著不同,并且这些变化在慢性缺氧时会改变。

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Lung endothelial cell proliferation in normal and pulmonary hypertensive neonatal calves.正常和患肺动脉高压新生犊牛的肺内皮细胞增殖
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Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells.JNK/c-Jun 的激活对于 EET 诱导的肺动脉内皮细胞增殖、存活和血管生成是必需的。
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