In vivo evidence of a delayed catabolism of remnant and decreased production of apoA-I in patients with chronic renal failure. -A stable isotope study.

慢性肾功能衰竭患者残余物分解代谢延迟和 apoA-I 产生减少的体内证据。

• 批准号: 11671054
• 负责人: IKEWAKI Katsunori
• 金额: $ 1.86万
• 依托单位: JIKEI UNIVERSITY, SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671054/
• 关键词: renal failure; hemodialysis; apolipoprotein; stable isotope

Atherosclerotic vascular disease frequently occurs in uremic patients receiving long-term hemodialysis (HD) and is the leading cause of death in these patients. Prominent characteristics of lipid abnormalities in HD patients is a decreased level of high density lipoprotein cholesterol and an increase in intermediate density lipoprotein (IDL) particle number. However, the exact mechanism for the decreased HDL cholesterol and increased IDL level remains unclear. In this kinetic study using stable isotope as a tracer, we wish to investigate apolipoprotein metabolism in 5 HD patients. 2H3-leucine was administered by a primed-constant infusion for 12 hrs and blood samples were collected up to 48 hrs. Tracer/tracee ratios of apoB-100 in very low density lipoprotein, IDL, low density lipoprotein and those of apoAI and AII in HDL were measured by gas-chromatography mass spectrometer, then integrated into a multicompartmental model to determine kinetic parameters. Although fractional catabolic rates (FCR) were, in general, decreased in HD patients, it was IDL apoB-100 showing the most profound decrease (70% decrease as compared to control subjects), resulting in the increased IDL apoB levels.VLDL and LDL ApoB levels remained normal due to an accompanying decrease in production rate. FCR of apoAI and apoA-II were similar to controls, whereas production rate of AII was decreased (p=0.05). In conclusions, these findings demonstrated, in vivo, that delayed catabolism of IDL apoB-100 and decreased production of apoA-II are main underlying defects leading to IDL accumulation and decreased HDL in HD patients.

动脉粥样硬化性血管疾病常见于接受长期血液透析（HD）的尿毒症患者，是这些患者死亡的主要原因。HD患者脂质异常的突出特征是高密度脂蛋白胆固醇水平降低，中密度脂蛋白（IDL）颗粒数增加。然而，HDL胆固醇降低和IDL水平升高的确切机制尚不清楚。在这个用稳定同位素作为示踪剂的动力学研究中，我们希望研究5例HD患者的载脂蛋白代谢。2h3 -亮氨酸以引物恒定输注12小时，采集血样至48小时。采用气相色谱质谱法测定极低密度脂蛋白、IDL、低密度脂蛋白中apoB-100的示踪/示踪率以及HDL中apoAI和AII的示踪/示踪率，并将其整合到多室模型中确定动力学参数。虽然HD患者的分数分解代谢率（FCR）总体上有所下降，但IDL apoB-100的下降最为显著（与对照组相比下降了70%），导致IDL apoB水平升高。VLDL和LDL载脂蛋白b水平保持正常，这是由于伴随的产率下降。apoAI和apoA-II的FCR与对照组相似，而AII的产率降低（p=0.05）。总之，这些研究结果表明，在体内，IDL的apoB-100分解代谢延迟和apoA-II的产生减少是导致HD患者IDL积累和HDL降低的主要潜在缺陷。