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首页> 外文期刊>Journal of vascular and interventional radiology: JVIR >Increased expression of HIF-1alpha, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency.
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Increased expression of HIF-1alpha, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency.

机译：在患有肾功能不全的小鼠模型中，动静脉瘘的静脉狭窄时，HIF-1α，VEGF-A及其受体，MMP-2，TIMP-1和ADAMTS-1的表达增加。

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PURPOSE: A mouse model of renal insufficiency with arteriovenous fistula (AVF) and venous stenosis was created. The authors tested the hypothesis that there is increased gene expression of hypoxia-inducible factor-1 alpha (HIF-1alpha); vascular endothelial growth factor-A (VEGF-A) and its receptors (VEGFR-1, -2); matrix metalloproteinase-2 (MMP-2), -9 (MMP-9); tissue inhibitor of metalloproteinase-1, -2 (TIMP-1, -2); and a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1) at the venous stenosis. MATERIALS AND METHODS: Nineteen male C57BL/6 mice underwent a left nephrectomy and a surgical occlusion of the right upper pole to induce renal function characterized in eight animals. Twenty eight days later, an AVF (n = 11) was created from the right carotid artery to ipsilateral jugular vein, and the mice were killed at day 7 (n = 4) and day 14 (n = 4). The outflow and control veins were removed for gene expression. Three mice were killed at day 28 for histologic analysis. RESULTS: The mean serum blood urea nitrogen level remained significantly elevated for 8 weeks when compared with baseline (P < .05). By day seven, there was a significant increase in the expression of HIF-1alpha, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein, with HIF-1alpha and TIMP-1 levels significantly elevated at day 14 (P < .05). By day 28, the venous stenosis was characterized by a thickened vein wall and neointima. CONCLUSIONS: A mouse model of renal insufficiency with AVF was developed that had increased expression of HIF-1alpha, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with venous stenosis by day 28.
机译：目的：创建了一种具有动静脉瘘（AVF）和静脉狭窄的肾功能不全的小鼠模型。作者检验了以下假设：缺氧诱导因子-1α（HIF-1alpha）的基因表达增加;血管内皮生长因子-A（VEGF-A）及其受体（VEGFR-1，-2）;基质金属蛋白酶2（MMP-2），-9（MMP-9）;金属蛋白酶-1，-2（TIMP-1，-2）的组织抑制剂;在静脉狭窄处有整合素和金属蛋白酶血小板反应蛋白-1（ADAMTS-1）。材料与方法：八只动物中有19只雄性C57BL / 6小鼠接受了左肾切除术和右上极的手术闭塞以诱导肾功能。二十八天后，从右颈动脉到同侧颈静脉建立了一个AVF（n = 11），并在第7天（n = 4）和第14天（n = 4）处死了小鼠。去除流出静脉和对照静脉用于基因表达。在第28天处死三只小鼠用于组织学分析。结果：与基线相比，平均血清尿素氮水平在8周内仍显着升高（P <.05）。到第七天，HIF-1alpha在流出静脉的表达明显增加，HIF-1alpha，VEGF-A，VEGFR-1，VEGFR-2，MMP-2，TIMP-1和ADAMTS-1和TIMP-1水平在第14天显着升高（P <.05）。到第28天，静脉狭窄的特征是静脉壁增厚和新内膜。结论：建立了AVF肾功能不全的小鼠模型，该模型在HIF-1α，VEGF-A，VEGFR-1，VEGFR-2，MMP-2，TIMP-1和ADAMTS-1的表达增加，并伴有AVF。第28天时出现静脉狭窄。

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