低白蛋白血症和蛋白尿分别导致肾病综合征中脂蛋白分解代谢降低。

Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome.

作者信息

Shearer G C, Stevenson F T, Atkinson D N, Jones H, Staprans I, Kaysen G A

机构信息

Division of Nephrology, Department of Medicine, UC Davis, Davis, CA 95616, USA.

出版信息

Kidney Int. 2001 Jan;59(1):179-89. doi: 10.1046/j.1523-1755.2001.00478.x.

DOI:10.1046/j.1523-1755.2001.00478.x

PMID:11135070

Abstract

BACKGROUND

Hypertriglyceridemia is a result of reduced triglyceride (TG)-rich lipoprotein (TRL) catabolism and occurs in rats with nephrotic syndrome (NS) and in Nagase analbuminemic rats (NARs). While the heparin-releasable lipoprotein lipase (LpL) pool in NAR and in NS is similar, TG levels are significantly greater in NS, suggesting that factors other than reduced LpL alone act in NS but not in NARs. Furthermore, clearance of chylomicrons (CM) and very low-density lipoprotein (VLDL) is normal in vivo in NAR despite low LpL levels. We tested the hypotheses that impaired binding of VLDL and impaired VLDL-high density lipoprotein (HDL) interactions contribute to hyperlipidemia in NS.

METHODS

TG and apoB secretion was measured using Triton WR 1339. Clearance of CMs by perfused hearts from NS and NAR was determined. Binding of VLDL from control, NS and NAR to rat aortic endothelial cells (RAECs) was measured prior to and following incubation with HDL from NS, NARs, and control. ApoE, protein, and TG content was determined.

RESULTS

TG levels were greatest in NS (516 +/- 95 mg/dL), intermediate in NAR (193 +/- 20), and least in control (97 +/- 16, P = 0.05), while in contrast, TG secretion was least in NS (178 +/- 33 mg/dL/hour) versus 212 +/- 17 in NAR and 294 +/- 15 in control (P < 0.001 vs. NS). Clearance of CMs by NS and NAR hearts was the same and significantly reduced versus control (P < 0.005). Binding of NS-VLDL to endothelial cells was reduced, while NAR-VLDL binding was increased versus control (P < 0.001). Incubation of NS-VLDL with control or NAR HDL increased VLDL binding compared with binding following incubation with NS HDL (P < 0.001).

CONCLUSION

Increased TG levels in both NS and NAR are the result of decreased TRL clearance. TG levels are greater in NS because of the presence of a combined defect: (1) a decrease in endothelial-bound LpL that occurs as a consequence of reduced serum albumin concentration, and (2) a defect in VLDL binding to endothelial-bound LpL. This latter defect occurs only in the presence of proteinuria and is conferred by HDL.

摘要

背景

高甘油三酯血症是富含甘油三酯（TG）的脂蛋白（TRL）分解代谢减少的结果，见于肾病综合征（NS）大鼠和长谷川无白蛋白血症大鼠（NAR）。虽然NAR和NS中肝素可释放的脂蛋白脂肪酶（LpL）储备相似，但NS中的TG水平显著更高，这表明除了LpL减少外，还有其他因素在NS中起作用，而在NAR中则不然。此外，尽管LpL水平较低，但NAR体内乳糜微粒（CM）和极低密度脂蛋白（VLDL）的清除正常。我们检验了以下假设：VLDL结合受损和VLDL与高密度脂蛋白（HDL）相互作用受损导致NS中的高脂血症。

方法

使用 Triton WR 1339 测量TG和载脂蛋白B（apoB）分泌。测定NS和NAR灌注心脏对CM的清除情况。在与NS、NAR和对照的HDL孵育之前和之后，测量对照、NS和NAR的VLDL与大鼠主动脉内皮细胞（RAEC）的结合。测定载脂蛋白E、蛋白质和TG含量。

结果

TG水平在NS中最高（516±95mg/dL），在NAR中居中（193±20），在对照中最低（97±16，P = 0.05），而相比之下，TG分泌在NS中最少（178±33mg/dL/小时），NAR中为212±17，对照中为294±15（与NS相比，P < 0.001）。NS和NAR心脏对CM的清除相同，且与对照相比显著降低（P < 0.005）。与对照相比，NS-VLDL与内皮细胞的结合减少，而NAR-VLDL结合增加（P < 0.001）。与用NS HDL孵育后的结合相比，用对照或NAR HDL孵育NS-VLDL增加了VLDL结合（P < 0.001）。