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人体锌代谢房室模型的建立:可识别性与多项研究分析

Development of a compartmental model of human zinc metabolism: identifiability and multiple studies analyses.

作者信息

Miller L V, Krebs N F, Hambidge K M

机构信息

Section of Nutrition, Department of Pediatrics and Center for Human Nutrition, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1671-84. doi: 10.1152/ajpregu.2000.279.5.R1671.

DOI:10.1152/ajpregu.2000.279.5.R1671
PMID:11049849
Abstract

A compartmental model of zinc metabolism has been developed from stable isotope tracer studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously, and the resulting enrichment was measured in plasma, erythrocytes, urine, and feces for as long as 3 wk. Data from total zinc measurements and model-independent calculations of various steady-state parameters were also modeled with the kinetic data. A structure comprised of 14 compartments and as many as 25 unknown kinetic parameters was developed to adequately model the data from each of the individual studies. The structural identifiability of the model was established using the GLOBI2 identifiability analysis software. Numerical identifiability of parameter estimates was evaluated using statistical data provided by SAAM. A majority of the model parameters was estimated with sufficient statistical certainty to be considered well determined. After the fitting of the model and data from the individual studies using SAAM/CONSAM, results were submitted to SAAM extended multiple studies analysis for aggregation into a single set of population parameters and statistics. The model was judged to be valid based on criteria described elsewhere.

摘要

通过对五名健康成年人进行稳定同位素示踪研究,建立了锌代谢的房室模型。口服和静脉注射多种同位素示踪剂,并在长达3周的时间内测量血浆、红细胞、尿液和粪便中的富集情况。来自总锌测量的数据以及各种稳态参数的非模型计算结果也与动力学数据一起进行建模。开发了一个由14个房室和多达25个未知动力学参数组成的结构,以充分模拟每个个体研究的数据。使用GLOBI2可识别性分析软件确定了模型的结构可识别性。使用SAAM提供的统计数据评估参数估计的数值可识别性。大多数模型参数的估计具有足够的统计确定性,可以认为是确定良好的。在使用SAAM/CONSAM对个体研究的模型和数据进行拟合后,将结果提交给SAAM扩展多研究分析,以汇总为一组单一的总体参数和统计数据。根据其他地方描述的标准,判断该模型是有效的。

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