MILK-BORNE GROWTH FACTORS FOR THE SUCKLING--THEIR EFFECTS ON NEONATE

乳汁生长因子——它们对新生儿的影响

• 批准号: 6341015
• 负责人: A F PHILIPPS
• 金额: $ 14.55万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341015
• 关键词: bile circulation; cell differentiation; cell growth regulation; developmental nutrition; dietary supplements; enzyme inhibitors; epidermal growth factor; exopeptidase; fatty acids; gastrointestinal function; gastrointestinal nutrient absorption; growth factor receptors; hormone regulation /control mechanism; insulinlike growth factor; laboratory rat; liver function; milk; newborn animals; nutrition related tag; oxidation reduction reaction; protein purification; receptor binding; tissue /cell culture

Growth Factors (GFs), such as Epidermal Growth Factor (EGF) and insulin- like Growth Factors (IGFs)-I and -II are present in most mammalian milks in concentrations sufficient to have biological effects. The preceding Project #1 (PI: O. Koldovsky) dealt with the sources of the mentioned GFs for the neonate. The purpose of this project is to examine the hypothesis that milk-borne GFs influence both growth and differentiation of the gastrointestinal tract (GI) of the suckling, and also have effects at sites distal to the GI tract. Studies dealing specifically with the effect on the liver and its function are the subject of Project #3 (PI: R. McCuskey). To test the hypothesis that milk-borne GFs affect the growth and development of the gastrointestinal (GI) tract and beyond, we will feed suckling rats either RMS or RMS supplemented with EGF, IGF-I and IGF- II individually, and in combination, in doses corresponding to the intake of these GF-s in milk. We hypothesize that feeding of GF-supplemented RMS to suckling rats will produce dose dependent changes in the growth of specific organs, including the liver, brain, cardiac and striated muscle, stomach and small bowel, and that IGFs and/or EGF fed to sucklings will stimulate cellular differentiation both locally (GI tract) and distally (eye, ear, etc.) To test the hypothesis that milk-borne GFs significantly alter a number of specific GI tract functions when given to the suckling chronically, we will study changes in several specific GI functions; namely, gastric evacuation, intestinal propulsive motility, and intestinal transport in suckling rats fed with RMS or RMS supplemented with GFs. Furthermore, we will explore the mechanisms involved in the absorption of GFs by the neonatal GI tract. The specificity of the inhibitable process for GF absorption from the GI tract will be tested by determining effects of excess EGF, TGFa, and IGFs on GF peptide absorption using the jejunal and ileal loop models of in vivo absorption. Since rat milk is known to contain factors that inhibit degradation of several peptide hormones by rat gastric and intestinal juices in vitro, we will characterize further (using HPLC) the fractions of rat milk responsible for this protective property and analyze their role in the mechanism of GI absorption of GF in suckling rats. We will also test the hypothesis that an enterohepatic circulation of IGFs exists, contributing to the increase of effectiveness of milk-borne and endogenously produced IGFs. Lastly, we will test the hypothesis that a milk-borne source of epidermal growth factor and insulin-like growth factors functions in the regulation of whole body long-chain fatty acid oxidation capacity in the suckling rat.

生长因子（GF），例如表皮生长因子（EGF）和胰岛素 - 像生长因子（IGFS）-i和-ii一样，大多数哺乳动物奶中存在 足以具有生物学作用的浓度。 前面 项目＃1（PI：O。Koldovsky）涉及上述GFS的来源 对于新生儿。 该项目的目的是检查假设 牛奶中的GFS影响着生长和分化 哺乳的胃肠道（GI），也有影响 地理区远端的地点。 专门针对的研究 对肝脏及其功能的影响是项目＃3的主题（PI：R。 麦考尼）。 为了测试牛奶 - 传播GF会影响生长的假设 以及胃肠道（GI）及其他地区的发展，我们将 喂食大鼠RMS或补充EGF，IGF-I和IGF-的RMS ii单独，组合，剂量与摄入量相对应 在牛奶中的这些GF-S中。 我们假设喂食GF补充的RMS 哺乳的大鼠将在生长的生长中产生剂量依赖性变化 特定的器官，包括肝脏，大脑，心脏和肌肉肌肉， 胃和小肠，喂食的IGF和/或EGF会浸泡 刺激局部和远端的细胞分化 （眼睛，耳朵等）测试牛奶 - 传播GFS的假设 当给予哺乳时，请更改许多特定的胃肠道功能 长期以来，我们将研究几种特定的GI功能的变化。 也就是说，胃疏散，肠道推进运动和肠道 用RMS或补充GFS的RMS喂食的哺乳老鼠的运输。 此外，我们将探索吸收的机制 新生儿胃肠道的GFS。 可约束过程的特异性 对于从胃肠道吸收的GF，将通过确定效应来测试 使用空肠的GF肽吸收过多的EGF，TGFA和IGF 和体内吸收的回肠环模型。 由于已知大鼠牛奶 包含抑制几种肽激素降解的因素 大鼠胃和肠汁在体外，我们将进一步表征 （使用HPLC）负责此保护性的老鼠牛奶的分数 财产并分析其在GF吸收GF机制中的作用 哺乳老鼠。 我们还将检验以下假设 存在IGF的循环，有助于提高有效性 牛奶播和内源性产生的IGF。 最后，我们将测试 假设表皮生长因子和 胰岛素样生长因子在整个身体的调节中起作用 哺乳大鼠的长链脂肪酸氧化能力。