ROLE OF MILK-BORNE SUBSTANCES IN DEVELOPING LIVER

乳源物质在肝脏发育中的作用

• 批准号: 6108544
• 负责人: ROBERT S MCCUSKEY
• 金额: $ 14.55万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108544
• 关键词: DNA replication; developmental nutrition; electron microscopy; epidermal growth factor; gene expression; glucokinase; glucose 6 phosphatase; glucose metabolism; histogenesis; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; insulinlike growth factor; laboratory rat; light microscopy; liver cells; liver function; messenger RNA; milk; newborn animals; northern blottings; nutrition related tag; prolactin

The overall aim of this study is to elucidate structural and functional differences in the development of the microvasculature and its surrounding parenchyma and cells in livers of suckling rats that may be attributed to the presence of hormones or hormone-like substances in breast milk. This is being accomplished using high resolution in vivo microscopic methods as well as light and electron microscopic morphometry of histologic, immunohistochemical, and in situ hybridization preparations. More specifically, the following parameters will be studied as a function of the presence or absence in an artificial milk diet of growth factors alone or in combination, e.g., epidermal growth factor (EGF), prolactin, and insulin-like growth factors (IGF I and II), which are transported biologically intact to the liver of suckling rats: (a) development of the hepatic microvascular system including patterns and rates of blood flow, dimensional changes in diameters, lengths and separation of vessels and reactivity to the test substances; (b) development of sinusoid wall structure including cellular composition as well as heterogeneity and function; (c) development of hepatic parenchymal cell organization into adult cell plates as reflected by DNA synthetic index, mitotic index, appearance of binucleated cells and structural heterogeneity; (d) development of functional heterogeneity for glucose metabolism in hepatic parenchymal cells as reflected in the expression of mRNA for the periportal enzyme, glucose-6-phosphatase G-6-Pase, and the centrilobular enzyme, glucokinase (GK), demonstrated by in situ hybridization. The results should help to elucidate the role(s) of these substances in affecting postnatal liver development during the suckling period. The results also ultimately may be useful in establishing the rationals for inclusion of some of these substances in proprietary infant milk formulas.

这项研究的总体目的是阐明结构和功能 微脉管系统及其周围的发展差异 哺乳大鼠肝脏中的实质和细胞可能归因于 在母乳中存在激素或激素样物质。 这 正在使用高分辨率在体内显微镜方法中完成 以及组织学的光和电子显微镜形态计量学 免疫组织化学和原位杂交制剂。 更多的 具体而言，将研究以下参数作为 仅生长因子的人造牛奶饮食中的存在或不存在 或组合，例如表皮生长因子（EGF），催乳素和 运输的胰岛素样生长因子（IGF I和II） 从生物学上完整到哺乳老鼠的肝脏：（a）发展 肝微血管系统，包括模式和血流速率， 直径，长度和分离容器和分离的维度变化 对测试物质的反应性； （b）正弦墙的发展 结构包括细胞组成以及异质性和 功能; （c）将肝实质细胞组织的发展开发 DNA合成指数，有丝分裂指数反映的成年细胞板， 双核细胞的出现和结构异质性； （D） 开发肝中葡萄糖代谢的功能异质性 实质细胞反映在mRNA表达中 外周酶，葡萄糖-6-磷酸酶G-6-Pase和Centrilobular 酶，葡萄糖激酶（GK），通过原位杂交证明。 这 结果应有助于阐明这些物质在 在哺乳期影响产后肝发育。 这 结果最终也可能对建立理由 将其中一些物质纳入专有婴儿奶制品中。