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.

动脉粥样硬化性血管疾病经常发生在接受长期血液透析(HD)的尿毒症患者中，是这些患者死亡的主要原因。HD患者血脂异常的显著特征是高密度脂蛋白胆固醇水平降低，中密度脂蛋白(IDL)颗粒增多。然而，高密度脂蛋白胆固醇降低和IDL水平升高的确切机制仍不清楚。在这项以稳定同位素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-亮氨酸持续输注12h，采集血样至48h。用气相色谱-质谱仪测定极低密度脂蛋白、低密度脂蛋白、低密度脂蛋白中apoB-100和高密度脂蛋白中载脂蛋白AI、AII的示踪/示踪比值，并结合多室模型确定动力学参数。虽然HD患者的分数分解代谢率(FCR)总体上降低，但IDL apoB-100的降低最为明显(与对照组相比下降了70%)，导致IDL apoB水平升高。由于伴随着产生率的下降，VLDL和LDL apoB水平保持正常。载脂蛋白AI和载脂蛋白A-II的FCR与对照组相似，而AII的生成率降低(P=0.05)。总之，这些发现表明，在体内，IDL apoB-100的延迟分解代谢和apoA-II的产生减少是导致HD患者IDL积聚和HDL值降低的主要潜在缺陷。

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.