Parenteral Administration of L-Arginine Prevents Fetal Growth Restriction in Undernourished Ewes

Parenteral Administration of L-Arginine Prevents Fetal Growth Restriction in Undernourished Ewes
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DOI:
10.3945/jn.110.125658
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发表时间:
2010-07-01
影响因子:
4.2
通讯作者:
Wu, Guoyao
Wu, Guoyao
中科院分区:
医学2区
文献类型:
--
作者:
Lassala, Arantzatzu;Bazer, Fuller W.;Wu, Guoyao

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宫内生长受限(IUGR)是一个全球性的主要健康问题,目前缺乏有效的治疗方案。本研究用绵羊IUGR模型来检验肠外给予L-精氨酸(Arg)对促进胎儿生长有效的假设。从妊娠第28天开始,母羊饲喂的饮食提供100%(对照喂养)或50%(喂养不足)的NRC推荐的营养需求。d 60之间的妊娠和分娩,营养不良的母羊接受静脉注射生理盐水或155 μ mol精氨酸盐酸/公斤体重,每天3次,而对照喂养的母羊只接受生理盐水。盐水灌注的营养不良母羊的羔羊出生体重比对照喂养的母畜的羔羊出生体重低23%(P< 0.01)。增加对营养不良母羊的精氨酸给药(P< 0.01)母体血清中精氨酸(169%)、鸟氨酸(155%)、脯氨酸(29%)、甲硫氨酸(37%)、亮氨酸(36%)、异亮氨酸(35%)、半胱氨酸(19%)和FFA(43%)的浓度降低了母体循环中氨(18%)和甘油三酯(32%)的水平,与盐水注入的营养不良母羊相比,羔羊的出生体重增加了21%。对照组和精氨酸输注组的羔羊出生体重无差异。这些新的结果表明,肠外给药精氨酸营养不良的母羊防止胎儿生长受限,并提供支持其临床应用,以改善IUGR的人。这一发现也为研究精氨酸在调节孕体生长和发育中的有益作用的细胞和分子机制奠定了新的框架。J.营养140:1242-1248,. 2010.
Intrauterine growth restriction (IUGR) is a major health problem worldwide that currently lacks an effective therapeutic solution. This study was conducted with an ovine IUGR model to test the hypothesis that parenteral administration of L-arginine (Arg) is effective in enhancing fetal growth. Beginning on d 28 of gestation, ewes were fed a diet providing 100% (control-fed) or 50% (underfed) of NRC-recommended nutrient requirements. Between d 60 of gestation and parturition, underfed ewes received i.v. infusions of saline or 155 mu mol Arg-HCl/kg body weight 3 times daily, whereas control-fed ewes received only saline. The birth weights of lambs from saline-infused underfed ewes were 23% lower (P< 0.01) than those of lambs from control-fed dams. Administration of Arg to underfed ewes increased (P< 0.01) concentrations of Arg 169%), ornithine 155%), proline (29%), methionine (37%), leucine (36%), isoleucine (35%), cysteine (19%), and FFA (43%) in maternal serum, decreased maternal circulating levels of ammonia (18%) and triglycerides (32%), and enhanced birth weights of lambs by 21% compared with saline-infused underfed ewes. There was no difference in birth weights of lambs between the control-fed and the Arg-infused underfed ewes. These novel results indicate that parenteral administration of Arg to underfed ewes prevented fetal growth restriction and provide support for its clinical use to ameliorate IUGR in humans. The findings also lay a new framework for studying cellular and molecular mechanisms responsible for the beneficial effects of Arg in regulating conceptus growth and development. J. Nutr. 140: 1242-1248,. 2010.