ZINC ABSORPTION IN ANIMAL MODELS OF CHILDHOOD DISEASE

儿童疾病动物模型中的锌吸收

• 批准号: 3322300
• 负责人: RAUL A WAPNIR
• 金额: $ 9.89万
• 依托单位: NORTH SHORE UNIVERSITY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1990-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3322300
• 关键词: aminoacid analyzer; baby food; basolateral membrane; brush border membrane; developmental nutrition; diarrhea; dietary supplements; dietary trace element; disease /disorder model; electrolyte balance; electron microscopy; gastrointestinal infection; gastrointestinal nutrient absorption; infant nutrition disorder; malnutrition; metal complex; metal metabolism; metal metabolism disorder; model design /development; nutrient interaction; nutrition related tag; radiotracer; small intestines; tissue /cell culture; zinc

Trace elements such as zinc are essential components of enzymes and proteins. In natural foods, zinc is generally tightly bound to macromolecules. We hypothesize that low molecular weight substances of dietary origin, or present in gastrointestinal secretions, are the vehicles for intestinal transport of zinc, through the formation of absorbable organometallic complexes. Appropriate absorption is particularly important early in life, when a lack of adequate supplies of vital nutrients may have long lasting consequences, and when childhood diseases may affect normal absorption. Our proposed research will focus on zinc chelates formed by some amino acids, dipeptides and organic acids known to, or estimated to form complexes with the lowest dissociation constants. These complexes are the ones most likely to penetrate the enterocyte by carrier mediated mechanisms and by solvent drag. We intend to perform quantitative absorption studies to determine the kinetics of the translocation processes operating in different areas of the gut, using the rat as our experimental species. The procedures will include open loop perfusions of the test solutions in anesthetized rats, everted intestinal rings and brush border membrane vesicles, plus separative techniques. This may enable us to assess the role of the brush border surface and the basolateral membrane of the absorptive cells on zinc uptake, and determine, with histochemical techniques, whether zinc is localized in particular compartments during its transport. We will also assess the interactions between macronutrients and zinc, and their effects on zinc absorption. We will study the uptake of zinc by the small intestinal mucosa under the following conditions: [a] in well nourished rats; [b] following the effects of chronic diarrhea; [c] under the influence of a deconjugated bile salt, which reflects the consequence of bacterial proliferation. The animal models to be utilized have already been tested in our own and other laboratories. Our data are expected to provide detailed information on the physiology of the luminal phase of zinc absorption in normal conditions, and in pathologic situations which frequently present early in life and which have a worldwide public health impact. Our findings may ultimately be used in the improvement of infant formulae, as well as in the preparations of dietary mineral supplements to alleviate nutritional deficits in children with conditions such as failure to thrive and diarrhea.

诸如锌之类的微量元素是酶的重要组成部分， 蛋白质。 在天然食品中，锌通常与 大分子。 我们假设低分子量的低分子量物质 饮食起源或胃肠道分泌物中存在的是车辆 通过可吸收的形成锌的肠运输 有机金属络合物。 适当的吸收特别重要 生命的早期，当缺乏足够的重要养分供应时 持久的后果以及童年疾病可能影响正常 吸收。 我们提出的研究将重点放在某些氨基的锌螯合物上 已知或估计形成的酸，二肽和有机酸 分离常数最低的复合物。 这些综合体是 最有可能通过载体介导的机制穿透肠肠细胞 并通过溶剂阻力。 我们打算进行定量吸收研究 确定在运行中运行的易位过程的动力学 肠道的不同区域，使用大鼠作为我们的实验物种。 这 程序将包括测试解决方案的开环灌注 麻醉大鼠，肠环和刷边缘膜 囊泡，以及分离技术。 这可能使我们能够评估 刷子边界表面和基底外侧膜的作用 锌吸收细胞，并用组织化学确定 技术，锌在其特定隔室中是否在其期间定位 运输。 我们还将评估大量营养素与锌之间的相互作用，以及 它们对锌吸收的影响。 我们将研究锌的吸收 在以下条件下的小肠粘膜小：[a]在井中 滋养老鼠； [b]遵循慢性腹泻的影响； [c]下 反映后果的变形胆汁盐的影响 细菌增殖。 要使用的动物模型已经 在我们自己和其他实验室中进行了测试。 期望我们的数据提供有关生理学的详细信息 锌吸收的腔阶段在正常条件下，在 病理状况经常出现在生活的早期，并且 全球公共卫生影响。 我们的发现最终可能用于 婴儿配方的改善以及 饮食中的矿物质补充剂以减轻儿童的营养缺陷 诸如未能繁殖和腹泻之类的条件。