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给妊娠大鼠喂食低蛋白饮食并补充牛磺酸可使胎儿内分泌胰腺的血管形成正常化。

Taurine supplementation of a low protein diet fed to rat dams normalizes the vascularization of the fetal endocrine pancreas.

作者信息

Boujendar Samira, Arany Edith, Hill David, Remacle Claude, Reusens Brigitte

机构信息

Laboratoire de Biologie Cellulaire, World Health Collaborating Center for the Development of the Endocrine Pancreas, Université Catholique de Louvain, B-1348 Louvain-La-Neuve, Belgium.

出版信息

J Nutr. 2003 Sep;133(9):2820-5. doi: 10.1093/jn/133.9.2820.

Abstract

In rats, an isoenergetic low protein diet (LP) given throughout gestation perturbs the development of the endocrine pancreas by reducing beta-cell mass and islet vascularization at birth. Taurine, an important amino acid during development, has been found to be low in fetal and maternal plasma. When added to a LP diet, taurine normalizes beta-cell mass. Therefore, we investigated the ability of taurine to correct altered islet vascularization. Rats were given 20% [control (C)] or 8% (LP) protein in the diet with or without supplementation with 25 g/L taurine (T) in drinking water (C+T and LP+T) during gestation and lactation. Immunostaining for vascular endothelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1), a VEGF receptor, was performed on fetal and neonatal pancreatic sections. Blood vessel density and blood vessel number were analyzed morphometrically on semi-thin sections. Taurine supplementation restored a normal volume and numerical density of vessels in fetal islets. The number of cells showing immunoreactivity for VEGF and Flk-1 was reduced by 33 and 45%, respectively, in islet cells from LP fetuses. In 1-mo-old pups, VEGF-positive cells remained decreased by nearly 22%. Both VEGF and Flk-1 were restored in pancreatic endocrine cells of fetuses and pups given taurine. The LP diet induced a threefold overexpression of Flk-1 in ductal cells, which contain precursors of beta cells. However, taurine supplementation was without effect. In conclusion, underexpression of VEGF and Flk-1 is associated with the lower fetal islet vascularization induced by the maternal malnutrition. The addition of taurine to the maternal diet prevents such damage and has a potential role in islet vasculogenesis.

摘要

在大鼠中,整个妊娠期给予等能量低蛋白饮食(LP)会通过减少出生时的β细胞量和胰岛血管形成来扰乱内分泌胰腺的发育。牛磺酸是发育过程中的一种重要氨基酸,已发现其在胎儿和母体血浆中的含量较低。当添加到LP饮食中时,牛磺酸可使β细胞量恢复正常。因此,我们研究了牛磺酸纠正胰岛血管形成改变的能力。在妊娠和哺乳期,给大鼠喂食含20%[对照(C)]或8%(LP)蛋白质的饮食,并在饮用水中添加或不添加25 g/L牛磺酸(T)(C+T和LP+T)。对胎儿和新生儿胰腺切片进行血管内皮生长因子(VEGF)和VEGF受体胎儿肝激酶-1(Flk-1)的免疫染色。在半薄切片上进行形态计量学分析血管密度和血管数量。补充牛磺酸可使胎儿胰岛中的血管体积和数量密度恢复正常。LP胎儿胰岛细胞中显示VEGF和Flk-1免疫反应性的细胞数量分别减少了33%和45%。在1月龄幼崽中,VEGF阳性细胞仍减少近22%。给予牛磺酸的胎儿和幼崽的胰腺内分泌细胞中VEGF和Flk-1均恢复正常。LP饮食诱导含有β细胞前体的导管细胞中Flk-1的表达增加了三倍。然而,补充牛磺酸没有效果。总之,VEGF和Flk-1的低表达与母体营养不良诱导的胎儿胰岛血管形成减少有关。在母体饮食中添加牛磺酸可预防这种损伤,并在胰岛血管生成中具有潜在作用。

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