ROLE OF MILK-BORNE SUBSTANCES IN DEVELOPING LIVER

乳源物质在肝脏发育中的作用

• 批准号: 6202071
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202071
• 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.

本研究的总体目标是阐明结构和功能 微血管及其周围组织发育的差异 乳鼠肝脏中的实质和细胞，可能归因于 母乳中存在激素或类似激素的物质。 这 是使用高分辨率的体内显微镜方法完成的， 光镜和电镜下组织学形态计量学， 免疫组织化学和原位杂交制备。 更 具体地说，将研究下列参数作为下列因素的函数： 在人造奶饮食中单独存在或不存在生长因子 或者组合，例如，表皮生长因子（EGF），催乳素， 胰岛素样生长因子（IGF I和II）， 生物学上完整的哺乳大鼠的肝脏：（a）发展的 肝微血管系统，包括血流模式和速率， 血管直径、长度和间隔的尺寸变化， 对供试品的反应性;（B）窦壁的发育 结构，包括细胞组成以及异质性， 功能;（c）肝实质细胞组织发育成 通过DNA合成指数，有丝分裂指数， 出现双核细胞和结构异质性;（d） 肝脏糖代谢功能异质性的研究进展 实质细胞的mRNA表达反映了 门脉周围酶、葡萄糖-6-磷酸酶G-6-磷酸酶和小叶中心酶 酶，葡萄糖激酶（GK），通过原位杂交证明。 的 结果应有助于阐明这些物质的作用， 在哺乳期影响出生后肝脏发育。 的 结果最终也可能有助于建立以下理由： 在专利婴儿配方奶粉中加入这些物质。