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雏鸡锶诱导佝偻病中25-羟基维生素D3代谢的动力学分析

Kinetic analysis of 25-hydroxyvitamin D3 metabolism in strontium-induced rickets in the chick.

作者信息

Omdahl J L, Jelinek G, Eaton R P

出版信息

J Clin Invest. 1977 Nov;60(5):1202-10. doi: 10.1172/JCI108873.

DOI:10.1172/JCI108873
PMID:908759
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC372474/
Abstract

Kinetic data analysis was used to derive a six-compartment computer model which describes the in vivo [3H]25-hydroxyvitamin D3 ([3H]25-OHD3) metabolism in control and strontium rachitic chicks. Plasma concentrations of 25-OHD3 (13 pmol/ml) and 25, 25-dihydroxyvitamin D3 (0.9 pmol/ml) were 18 and 125% greater than controls, respectively, whereas the corresponding level for 1alpha,25-dihydroxyvitamin D3 (0.3 pmol/ml) was only 30% of control. Plasma disappearance of 25-HOD3 was fitted using a two-compartment model in which the metabolite extrapolated half-life was nearly twice as large for strontium rachitic chicks (71 compared to 41 h). Intestinal sequestration of 1alpha,25-dihydroxyvitamin D3 was assumed to be irreversible and was fitted by a single exponential term in which metabolite uptake rate and tissue concentration in strontium rickets was suppressed to 20 and 10% of control, respectively. In contrast, uptake of 25-OHD3 by the intestine was observed to occur by a reversible process in which metabolite concentration was 45% greater in the strontium rachitic compared to control group. The developed compartment model accepts time-dependent control or perturbed metabolite data for the plasma and (or) intestinal pools and provides quantitative values for metabolite pool size, flux rate, and turnover time.

摘要

动力学数据分析被用于推导一个六室计算机模型,该模型描述了正常和锶致佝偻病雏鸡体内[3H]25-羟基维生素D3([3H]25-OHD3)的代谢情况。25-OHD3(13 pmol/ml)和25,25-二羟基维生素D3(0.9 pmol/ml)的血浆浓度分别比正常组高18%和125%,而1α,25-二羟基维生素D3(0.3 pmol/ml)的相应水平仅为正常组的30%。25-HOD3的血浆清除率采用二室模型拟合,其中该代谢产物的外推半衰期在锶致佝偻病雏鸡中几乎是正常雏鸡的两倍(分别为71小时和41小时)。假定1α,25-二羟基维生素D3在肠道的潴留是不可逆的,并通过一个单指数项拟合,其中在锶佝偻病雏鸡中代谢产物的摄取率和组织浓度分别被抑制至正常组的20%和10%。相反,观察到肠道对25-OHD3的摄取是一个可逆过程,其中与正常组相比,锶致佝偻病雏鸡中的代谢产物浓度高45%。所建立的室模型接受血浆和(或)肠道库随时间变化的正常或受干扰的代谢产物数据,并提供代谢产物库大小、通量率和周转时间的定量值。

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本文引用的文献

1
Some formal approaches to the analysis of kinetic data in terms of linear compartmental systems.一些根据线性房室系统对动力学数据进行分析的形式化方法。
Biophys J. 1962 May;2(3):289-316. doi: 10.1016/s0006-3495(62)86856-8.
2
The routine fitting of kinetic data to models: a mathematical formalism for digital computers.动力学数据与模型的常规拟合:一种适用于数字计算机的数学形式体系。
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Biologically active metabolite of vitamin D3 from bone, liver, and blood serum.来自骨骼、肝脏和血清的维生素D3的生物活性代谢物。
J Lipid Res. 1966 Nov;7(6):739-44.
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Distribution and turnover of cholesterol in humans.人体中胆固醇的分布与周转
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25-Hydroxycholecalciderol dynamics in human plasma.
Rev Eur Etud Clin Biol. 1972 Oct;17(8):793-6.
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1Alpha-hydroxyvitamin D3. An analog of vitamin D which apparently acts by metabolism to 1alpha, 25-dihydroxyvitamin D3.
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7
Effects of nucleotides, hormones, ions, and 1,25-dihydroxycholecalciferon on 1,25-dihydroxycholecalciferol production in isolated chick renal tubules.核苷酸、激素、离子及1,25 - 二羟胆钙化醇对离体鸡肾小管中1,25 - 二羟胆钙化醇生成的影响。
Clin Sci Mol Med. 1974 May;46(5):569-82. doi: 10.1042/cs0460569.
8
A rapid assay for 25-OH-vitamin D3 without preparative chromatography.一种无需制备色谱法的25-羟基维生素D3快速检测方法。
J Clin Endocrinol Metab. 1974 Jun;38(6):1046-51. doi: 10.1210/jcem-38-6-1046.
9
A new chromatographic system for vitamin D3 and its metabolites: resoluation of a new vitamin D3 metabolite.一种用于维生素D3及其代谢物的新型色谱系统:一种新的维生素D3代谢物的分离
J Lipid Res. 1971 Jul;12(4):460-5.
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1 Alpha,25-dihydroxycholecalciferol receptors in intestine. II. Temperature-dependent transfer of the hormone to chromatin via a specific cytosol receptor.1 肠道中的α,25-二羟胆钙化醇受体。II. 激素通过特定胞质溶胶受体向染色质的温度依赖性转移。
J Biol Chem. 1974 Feb 25;249(4):1258-62.