Intestinal vascular endothelial growth factor is decreased in necrotizing enterocolitis.

Intestinal vascular endothelial growth factor is decreased in necrotizing enterocolitis.
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肠道血管内皮生长因子在坏死性小肠结肠炎中降低。

DOI:
10.1159/000368879
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发表时间:
2015
期刊:
影响因子:
2.5
通讯作者:
De Plaen IG
De Plaen IG
中科院分区:
医学2区
文献类型:
--
作者:
Sabnis A;Carrasco R;Liu SX;Yan X;Managlia E;Chou PM;Tan XD;De Plaen IG

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肠道灌注减少可能导致坏死性小肠结肠炎(NEC)的发生。血管内皮生长因子(VEGF)是毛细血管网络发育和维持所必需的血管生成蛋白。 NEC 中 VEGF 是否失调仍不清楚。确定 NEC 新生小鼠模型和人类 NEC 患者肠道 VEGF 表达是否发生改变。我们首先评估了新生小鼠 NEC 模型中发生重大损伤之前肠道 VEGF mRNA 和蛋白质的变化。然后我们检查了配方奶喂养、细菌接种、冷应激和/或间歇性缺氧是否影响肠道 VEGF 表达。最后,我们通过免疫组织化学观察了小鼠和人类 NEC 以及对照病例肠道组织中的 VEGF 蛋白。与对照组相比,接受 NEC 方案的幼犬肠道 VEGF 蛋白和 mRNA 显着减少。缺氧、冷应激和共生细菌一起给药时,显着下调肠道 VEGF 表达,而单独给药时没有显着影响。 VEGF 定位于少数单个肠上皮细胞以及固有层和肌间神经丛的一些细胞。与对照组织相比,鼠和人 NEC 肠道中 VEGF 染色减少。人类和实验 NEC 中肠道 VEGF 蛋白减少。 VEGF 产生减少可能导致 NEC 发病机制。
Decreased intestinal perfusion may contribute to the development of necrotizing enterocolitis (NEC). Vascular endothelial growth factor (VEGF) is an angiogenic protein necessary for the development and maintenance of capillary networks. Whether VEGF is dysregulated in NEC remains unknown. To determine whether intestinal VEGF expression is altered in a neonatal mouse model of NEC and in human NEC patients. We first assessed changes of intestinal VEGF mRNA and protein in a neonatal mouse NEC model before significant injury occurs. We then examined whether exposure to formula feeding, bacterial inoculation, cold stress and/or intermittent hypoxia affected intestinal VEGF expression. Last, we visualized VEGF protein in intestinal tissues of murine and human NEC and control cases by immunohistochemistry. Intestinal VEGF protein and mRNA were significantly decreased in pups exposed to the NEC protocol, compared to controls. Hypoxia, cold stress and commensal bacteria, when administered together, significantly downregulated intestinal VEGF expression, while they had no significant effect when given alone. VEGF was localized to few single intestinal epithelial cells and some cells of the lamina propria and myenteric plexus. VEGF staining was decreased in murine and human NEC intestines when compared to control tissues. Intestinal VEGF protein is reduced in human and experimental NEC. Decreased VEGF production might contribute to NEC pathogenesis.
DOI: 10.1159/000351040
发表时间: 2013-01-01
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