MINIMAL ENTERAL NUTRIENT REQUIREMENTS IN NEONATES

长期目标是定量肠内营养素 新生儿肠道生长和功能的要求，并确定 调节肠道营养反应的细胞机制。工作 在拟议的研究中概述的将测试四个假设：1）保持 GLP-2的循环浓度在典型的肠内喂养的水平 猪，将恢复肠道生长和结构的TPN喂养的新生猪。（二） 在该生理范围内，GLP-2急性激活细胞信号传导 导致抑制肠蛋白水解和细胞凋亡的途径， 并且这些细胞过程是肠道的主要介质 GLP-2的营养作用。3)GLP-2生理水平的维持 在一段时间的TPN将上调肠道乳糖的能力 消化和葡萄糖吸收。4)在子宫内，胎儿的肠道 对GLP-2无反应。这些假设将使用主题方案网络反馈的方法进行检验， 初乳剥夺，新生猪模型，这些目的：目的1：量化 GLP-2对肠质量和形态的生理剂量反应。目标二： 确定蛋白酶基因（溶酶体， 泛素-蛋白酶体和钙激活）和凋亡的活性 猪的信号通路中间体（Pl-3激酶/PKB、Bcl-2、半胱天冬酶） 用生理GLP-2剂量输注3、6或48小时。此外，为了衡量 肠蛋白质合成和蛋白水解的体内动力学，基于 GLP-2给药6、48和168小时后13 C-苯丙氨酸的门静脉平衡 输液目的3：测定刷状缘和基底外侧膜葡萄糖 转运活性以及乳糖酶、SGLT-1和 基于13 C/H-亮氨酸掺入的动力学， 生理GLP-2剂量持续7天。此外，测量在体内动力学的 肠道乳糖消化和葡萄糖吸收，基于门户网站 给予生理GLP-2剂量的猪中半乳糖和13 C-葡萄糖的平衡 7天。目的4：测定肠道营养（蛋白质代谢/细胞 周转）和功能（乳糖酶/葡萄糖转运活性）的反应性， 给予胎猪（子宫内）和新生猪的生理GLP-2剂量， 106和112天胎龄。

The long-term goals are to quantify the enteral nutrient requirements for neonatal intestinal growth and function and identify the cellular mechanisms that mediate the intestinal trophic response. The work outlined in the proposed studies will test four hypotheses: 1) Maintaining the circulating concentration of GLP-2 at a level typical of the enterally fed pigs, will restore intestinal growth and structure in TPN-fed neonatal pigs. 2) Within this physiological range, GLP-2 acutely activates cellular signaling pathways that lead to a suppression of intestinal proteolysis and apoptosis, and that these cellular processes are the primary mediators of the intestinal trophic effects of GLP-2. 3) The maintenance of physiological levels of GLP-2 during a period of TPN will up regulate the intestinal capacity of lactose digestion and glucose absorption. 4) In utero, the fetal intestine is unresponsive to GLP-2. These hypotheses will be tested using a TPN-fed, colostrum-deprived, neonatal pig model with these aims: Aim 1: Quantify the physiological dose response of GLP-2 on intestinal mass and morphology. Aim 2: Determine the intestinal expresson of protease genes (lysosomal, ubiquitin-proteasomal, and calcium-activated) and activity of apoptotic signaling pathway intermediataes (Pl-3 kinase/PKB, Bcl-2, caspases) in pigs infused with physiological GLP-2 dose for 3, 6, or 48 hours. Also, to measure the in vivo kinetics of intestinal protein synthesis and proteolysois, based on the portal balance of 13C-phenylalanine, after 6, 48, and 168 hours of GLP-2 infusion. Aim 3: Determine the brush-border and basolateral membrance glucose transport activity and the abundance and synthesis rate of lactase, SGLT-1 and GLUT2, based on the kinetics of 13C/H-leucine incorporation, in pigs given a physiological GLP-2 dose for 7 days. Also, measure the in vivo kinetics of intestinal lactose digestion and glucose absorption, based on the portal balance of galactose and 13C-glucose, in pigs given physiological GLP-2 dose for 7 days. Aim 4: Determine the intestinal trophic (protein metabolism/cell turnover) and functional (lactase/glucose transport activity) responsiveness to a physiological GLP-2 dose given to fetal (in utero) and newborn pigs between 106 and 112 days gestational age.