开发房室模型以研究炎症对应用视黄醇同位素稀释法预测理论人体维生素 A 全身储存量的影响。

Development of a Compartmental Model to Investigate the Influence of Inflammation on Predictions of Vitamin A Total Body Stores by Retinol Isotope Dilution in Theoretical Humans.

机构信息

Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.

出版信息

J Nutr. 2021 Mar 11;151(3):731-741. doi: 10.1093/jn/nxaa407.

BACKGROUND

Inflammation, both acute and chronic, is associated with reductions in the synthesis of retinol-binding protein (RBP) and the concentration of retinol in plasma. Consequently, it is currently recommended that the retinol isotope dilution (RID) method not be used to estimate vitamin A total body stores (TBS) in subjects with inflammation.

OBJECTIVES

To apply compartmental analysis to study the effects of inflammation on hepatic apo-RBP input, plasma retinol pool size, and RID-predicted TBS in theoretical subjects with known steady state values for these parameters.

METHODS

We selected 6 previously generated hypothetical subjects who ingested a dose of stable isotope-labeled vitamin A (day 0). Starting with each subject's published steady state model for retinol tracer kinetics, we developed a parallel model for unlabeled retinol and RBP that incorporated links between these entities and tied liver retinol secretion to RBP availability. Then we perturbed the steady state model by initiating chronic or acute inflammation on day 0 or acute inflammation on day 3 or 9 and simulating results for RBP, plasma retinol, and TBS.

RESULTS

Chronic inflammation led to substantial reductions in RID-predicted TBS for at least 2 weeks after tracer administration. In contrast, acute inflammation induced on day 0 or 3 resulted in less dramatic impacts on TBS (37% or 20% reduction, respectively, from steady state levels, with levels rebounding by 14 days). When inflammation was induced 9 days after administration of the tracer, the effects on predicted TBS were minimal. Overall, for acute inflammation initiated at 0, 3, or 9 days, accurate predictions of TBS were obtained by 2 weeks.

CONCLUSIONS

Compartmental analysis can be applied in the novel way described here to study the influence of perturbations such as inflammation on predictions of vitamin A status using RID. Such an approach has potential value for studying other perturbations and different nutrients.

背景

炎症，无论是急性还是慢性，都会导致视黄醇结合蛋白 (RBP) 的合成减少以及血浆中视黄醇的浓度降低。因此，目前建议不要使用视黄醇同位素稀释 (RID) 法来估计有炎症的受试者的维生素 A 全身总储存量 (TBS)。

目的

应用房室分析研究炎症对肝脏 apo-RBP 输入、血浆视黄醇库大小以及 RID 预测 TBS 的影响，这些参数在理论受试者中具有已知的稳态值。

方法

我们选择了 6 名先前生成的假设受试者，他们摄入了稳定同位素标记的维生素 A 剂量（第 0 天）。从每个受试者的发表的稳态视黄醇示踪剂动力学模型开始，我们开发了一个与未标记的视黄醇和 RBP 并行的模型，该模型将这些实体之间的联系结合起来，并将肝脏视黄醇分泌与 RBP 的可用性联系起来。然后，我们通过在第 0 天或第 3 天或第 9 天开始慢性或急性炎症，并模拟 RBP、血浆视黄醇和 TBS 的结果，来干扰稳态模型。

结果

慢性炎症导致 RID 预测 TBS 在示踪剂给药后至少 2 周内大幅减少。相比之下，第 0 天或第 3 天诱导的急性炎症对 TBS 的影响较小（分别比稳态水平减少 37%或 20%，到第 14 天恢复）。当在示踪剂给药后第 9 天诱导炎症时，对预测 TBS 的影响最小。总体而言，对于在第 0、3 或 9 天开始的急性炎症，在 2 周内可以准确预测 TBS。