A KINETIC STUDY OF INFLAMMATION-INDUCED HYPORETINEMIA

炎症引起的低蛋白血症的动力学研究

基本信息

  • 批准号:
    6887731
  • 负责人:
  • 金额:
    $ 13.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-08-04 至 2005-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to examine the consequences of inflammation-induced hyporetinemia on hepatic vitamin A (VA) stores and retinal function. Previously, it has been demonstrated that the synthesis of hepatic retinol-binding protein (RBP) and transthyretin (TTR) are reduced during acute inflammation causing a reduction of plasma retinol concentrations (hyporetinemia). The premise of the current study is that hyporetinemia, if prolonged, will impair the distribution of VA between hepatic and non-hepatic tissues. Two studies are proposed. In the first, the distribution and kinetic behavior of plasma retinol will be evaluated using kinetic data and model-based compartmental analysis during acute inflammation. Plasma containing labeled retinol {[3H]retinoI-RBP-TTR} will be injected iv to marginally-VA deficient rats and circulating tracer concentrations will be allowed to reach a terminal slope; then, the system will be perturbed by inducing acute inflammation with lipopolysaccharide from P. aeruginosa, and circulating tracer concentrations will be allowed to reach a new terminal slope. Tracer and tracee data will be collected from plasma, liver, kidneys, eyeballs and remaining carcass. Model-based compartmental analysis using the Simulation, Analysis and Modeling (SAAM) computer program will be used to adjust model parameters to best fit the data. Based on this analysis, hypotheses will be generated to explain the dynamics of pools of retinol among plasma, liver and kidneys, and how alterations in these pools may contribute to decrease retinal VA. in the second study, an animal model of chronic inflammation will be developed with continuous administration of recombinant human intedeukin-6 (rhlL6) to assess the effect of hyporetinemia on retinal function. Marginally-VA deficient rats will receive rhlL6 or saline by means of osmotic pumps for 7 to 14 d. VA concentrations in hepatic and non-hepatic tissues will be determined by HPLC at various times. Retinal function will be examined by means of electroretinography during the first and second weeks of experimentation. This information will help in re-defining VA status in the presence of low circulating retinol concentrations during inflammation. In addition, the application of these methods and the development of a model of chronic inflammation will foster research on other micronutrients like iron and zinc that are similarly affected by inflammation.
描述(由申请人提供): 这项建议的长期目标是研究炎症诱导的低视网膜血症对肝脏维生素A(VA)储存和视网膜功能的影响。以前,已经证明在急性炎症期间肝视黄醇结合蛋白(RBP)和甲状腺素运载蛋白(TTR)的合成减少,导致血浆视黄醇浓度降低(低视黄醇血症)。本研究的前提是,低视网膜血症,如果延长,将损害肝和非肝组织之间的VA分布。提出了两项研究。首先,在急性炎症期间,将使用动力学数据和基于模型的房室分析来评价血浆视黄醇的分布和动力学行为。将含有标记的视黄醇{[3 H]retinoI-RBP-TTR}的血浆静脉注射至边缘性VA缺乏大鼠,并使循环示踪剂浓度达到终末斜率;然后,通过用铜绿假单胞菌的脂多糖诱导急性炎症来扰乱系统,并使循环示踪剂浓度达到新的终末斜率。将从血浆、肝脏、肾脏、眼球和剩余尸体中采集示踪剂和示踪剂数据。将使用模拟、分析和建模(SAAM)计算机程序进行基于模型的房室分析,以调整模型参数,使其最佳拟合数据。基于该分析,将产生假设来解释血浆、肝脏和肾脏中视黄醇池的动力学,以及这些池中的改变如何有助于降低视网膜VA。在第二项研究中,将通过连续施用重组人白介素-6(rhIL-6)来建立慢性炎症的动物模型,以评估低视网膜血症对视网膜功能的影响。轻度VA缺乏的大鼠将通过渗透泵接受rhIL 6或盐水7至14天。将在不同时间通过HPLC测定肝脏和非肝脏组织中的VA浓度。在实验的第一周和第二周期间,将通过视网膜电图检查视网膜功能。这一信息将有助于在炎症期间低循环视黄醇浓度的情况下重新定义VA状态。此外,这些方法的应用和慢性炎症模型的开发将促进对其他微量营养素(如铁和锌)的研究,这些微量营养素也会受到炎症的影响。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Plasma alpha1-acid glycoprotein can be used to adjust inflammation-induced hyporetinolemia in vitamin A-sufficient, but not vitamin A-deficient or -supplemented rats.
血浆 α1-酸性糖蛋白可用于调节维生素 A 充足但维生素 A 缺乏或补充的大鼠中炎症引起的低视黄醇血症。
  • DOI:
    10.1093/jn/136.7.1904
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Gieng,SinH;Rosales,FranciscoJ
  • 通讯作者:
    Rosales,FranciscoJ
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FRANCISCO J ROSALES其他文献

FRANCISCO J ROSALES的其他文献

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{{ truncateString('FRANCISCO J ROSALES', 18)}}的其他基金

ASSESSMENT AND DETERMINATION OF BIOMARKERS OF INFLAMMATION IN URINE SAMPLES
尿液样本中炎症生物标志物的评估和测定
  • 批准号:
    7378537
  • 财政年份:
    2006
  • 资助金额:
    $ 13.22万
  • 项目类别:
ASSESSMENT AND DETERMINATION OF BIOMARKERS OF INFLAMMATION IN URINE SAMPLES
尿液样本中炎症生物标志物的评估和测定
  • 批准号:
    7203586
  • 财政年份:
    2005
  • 资助金额:
    $ 13.22万
  • 项目类别:
KINETIC STUDY OF INFLAMMATION-INDUCED HYPORETINEMIA
炎症引起的低蛋白血症的动力学研究
  • 批准号:
    6679389
  • 财政年份:
    2003
  • 资助金额:
    $ 13.22万
  • 项目类别:
A KINETIC STUDY OF INFLAMMATION-INDUCED HYPORETINEMIA
炎症引起的低蛋白血症的动力学研究
  • 批准号:
    6787273
  • 财政年份:
    2003
  • 资助金额:
    $ 13.22万
  • 项目类别:
Analysis of Retinol-Binding Protein Transthyretin
视黄醇结合蛋白转甲状腺素蛋白的分析
  • 批准号:
    7044456
  • 财政年份:
    2003
  • 资助金额:
    $ 13.22万
  • 项目类别:
MECHANISM OF INFLAMMATION INDUCED HYPORETINEMIA
炎症引起低蛋白血症的机制
  • 批准号:
    2015762
  • 财政年份:
    1997
  • 资助金额:
    $ 13.22万
  • 项目类别:
MECHANISM OF INFLAMMATION INDUCED HYPORETINEMIA
炎症引起低蛋白血症的机制
  • 批准号:
    2136104
  • 财政年份:
    1996
  • 资助金额:
    $ 13.22万
  • 项目类别:
MECHANISM OF INFLAMMATION INDUCED HYPORETINEMIA
炎症引起低蛋白血症的机制
  • 批准号:
    2136103
  • 财政年份:
    1994
  • 资助金额:
    $ 13.22万
  • 项目类别:

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