Development of a compartmental model of zinc kinetics in mice.

Development of a compartmental model of zinc kinetics in mice.
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DOI:
10.3945/jn.108.091504
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发表时间:
2008-11
影响因子:
4.2
通讯作者:
House, William A.
House, William A.
中科院分区:
医学2区
文献类型:
--
作者:
Wastney, Meryl E.;House, William A.

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为了研究小鼠体内锌(Zn)的动力学,给9周龄雌性小鼠在进食状态下口服示踪剂(65 Zn),并在随后的8 d内测量21个组织中的示踪剂和Zn浓度。使用WinSAAM通过房室模型分析数据。对已发表的大鼠锌动力学模型进行了修改,以拟合小鼠的数据,并计算锌的转移速率和池大小。在缺乏金属硫蛋白(MT)、MT-I和MT-II(MT-/-)基因的小鼠中进行了平行研究,以量化体内不存在这些蛋白质时锌动力学的差异。我们证实,在野生型小鼠和缺乏MT的小鼠中,大多数组织中的示踪剂时间过程是相似的,除了MT−/−的胰腺,它保留了较少的示踪剂。通过同时拟合组织和肠道数据,我们发现肠道示踪剂可以用未吸收的同位素来解释,并且从胰腺损失的锌通过血浆。MT-/-胰腺数据的差异可以通过该组织中锌的周转速度(4小时)是野生型(9小时)的两倍来解释。这些动力学研究为正常进食小鼠提供了参数值,其可用于评估异常条件下的Zn动力学,如MT敲除小鼠胰腺中Zn的更高周转所证明的。
To investigate zinc (Zn) kinetics in mice, tracer (65Zn) was administered orally to 9-wk-old female mice in the fed state and tracer and Zn concentration were measured in 21 tissues over the following 8 d. Data were analyzed by compartmental modeling using WinSAAM. A published model for Zn kinetics in rats was modified to fit the data from mice and to calculate transfer rates and pool sizes of Zn. Parallel studies were performed in mice lacking genes for metallothionein (MT), MT-I and MT-II (MT−/−), to quantify differences in Zn kinetics in the absence of these proteins in vivo. We confirmed that tracer time course in most tissues was similar in wild-type mice and those lacking MT, except for the pancreas of MT−/−, which retained less tracer. By fitting tissue and intestinal data simultaneously, we found that intestinal tracer could be explained by unabsorbed isotope and loss of Zn from pancreas went through plasma. Differences in pancreatic data in MT−/− were explained by Zn turning over twice as fast in this tissue (4 h) compared with wild type (9 h). These kinetic studies provide parameter values for normal, fed mice that can be used to assess Zn kinetics in abnormal conditions, as demonstrated by the higher turnover of Zn in the pancreas of MT knockout mice.
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