Department of Pediatrics, Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam 3015 GJ, The Netherlands.
J Nutr. 2011 Jan;141(1):63-70. doi: 10.3945/jn.110.131888. Epub 2010 Nov 24.
Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemia-reperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME). Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100-250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L⋅kg(-1)⋅h(-1)) pigs than in the TPN pigs (1.23 ± 0.17 L⋅kg(-1)⋅h(-1)), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent.
精氨酸是新生儿必需的氨基酸，由肠道上皮细胞合成，是调节血管舒张和血流的一氧化氮的前体。补充精氨酸已被证明可改善缺血再灌注模型中的肠道完整性，且低血浆水平与坏死性小肠结肠炎有关。我们假设，在全胃肠外营养（TPN）或部分胃肠外营养（PEN）条件下，肠内精氨酸是新生儿肠道血流和黏膜生长的特定刺激物。我们首先测试了急性（3 小时）肠内精氨酸输注对接受 TPN 或 PEN 喂养的猪肠系膜上动脉（SMA）血流的剂量依赖性和特异性。然后，我们确定了 PEN 中慢性（4 天）精氨酸补充是否增加了黏膜生长，以及这种情况是否受到一氧化氮合酶抑制剂 N(G)-硝基-l-精氨酸甲酯（L-NAME）的影响。急性肠内精氨酸输注可使 TPN 和 PEN 组的血浆精氨酸剂量依赖性增加，但 PEN 组的血浆反应在 2 种最高精氨酸剂量下比 TPN 组高（100-250%）。PEN 组（2.37 ± 0.32 L⋅kg(-1)⋅h(-1)）的 SMA 血流基线比 TPN 组（1.23 ± 0.17 L⋅kg(-1)⋅h(-1)）高 90%，但单独输注精氨酸、瓜氨酸或其他主要肠道燃料对其没有影响。PEN 组猪的慢性饮食精氨酸补充可诱导肠道黏膜生长，但 L-NAME 治疗并未预防这种作用。肠道隐窝细胞增殖、蛋白质合成以及哺乳动物雷帕霉素靶蛋白和 p70S6 激酶的磷酸化不受饮食精氨酸的影响。我们的结论是，部分胃肠外喂养而非急性肠内精氨酸可增加新生仔猪的 SMA 血流。此外，在部分胃肠外喂养中补充精氨酸可适度增加肠道黏膜生长，且与一氧化氮无关。
