Levy E, Ziv E, Bar-On H, Shafrir E
Department of Biochemistry, Hadassah University Hospital, Jerusalem, Israel.
Biochim Biophys Acta. 1990 Apr 17;1043(3):259-66. doi: 10.1016/0005-2760(90)90025-s.
Lymph chylomicrons and plasma VLDL, 14C-labelled in vivo, were isolated from normal and nephrotic rats and injected into normal or nephrotic recipients. In normal recipients, the half-life of chylomicrons of nephrotic vs. normal origin was significantly longer (5.2 +/- 0.5 vs. 3.5 +/- 0.4 min-1). The nephrotic chylomicrons were larger in size, deficient in apo-E and apo A-I, rich in triacylglycerol and cholesterol, but poor in phospholipids, indicating that factors related to composition affected their removal. The half-life of nephrotic vs. normal VLDL, given to normal recipients, was unexpectedly shorter, (4.5 +/- 0.2 vs. 5.8 +/- 0.2 min-1). The nephrotic VLDL were also triacylglycerol- and cholesterol-rich and phospholipid-poor, but had a large diameter spread and contained a dense fraction according to the zonal ultracentrifugation pattern, suggesting the presence of faster removable IDL-like particles. When nephrotic rats received normal particles, a pronounced removal delay was seen, paralleling the extent of plasma triacylglycerol elevation. The half-life of chylomicrons was 8.3 +/- 1.4 and 15.2 +/- 2.5 min-1 in moderately and severely nephrotic rats, respectively, that of VLDL was 11.72 +/- 2.1 and 37.8 +/- 7.1 min-1 correspondingly. The chylomicron-triacylglycerol uptake was reduced both by adipose tissues and muscles of normal or nephrotic recipients, with some increase in entry into lungs, kidneys and spleen. Tissue distribution patterns of VLDL-triacylglycerol was similar to that of chylomicrons, except that the liver took up approx. 90% of the label. The low share of triacylglycerol uptake by tissues rich in lipoprotein lipase indicates that the activity of this enzyme was unlikely to limit the rate of removal. Lipoprotein lipase activity in adipose tissue and heart was slightly decreased in moderately nephrotic rats and declined only by approx. 35% in severely nephrotic ones. These results indicate that the removal defect in nephrosis seems to be due, in part, to changes in the composition of triacylglycerol-rich particles, compromising their accessibility to lipolysis and, in part, to their abundance, saturating the lipolytic capacity.
从正常大鼠和肾病大鼠体内分离出经体内14C标记的淋巴乳糜微粒和血浆极低密度脂蛋白（VLDL），并注入正常或肾病受体。在正常受体中，肾病来源的乳糜微粒与正常来源的乳糜微粒相比，半衰期显著延长（5.2±0.5对3.5±0.4分钟-1）。肾病乳糜微粒尺寸更大，缺乏载脂蛋白E和载脂蛋白A-I，富含三酰甘油和胆固醇，但磷脂含量低，这表明与组成相关的因素影响了它们的清除。给予正常受体时，肾病VLDL与正常VLDL相比，半衰期意外缩短（4.5±0.2对5.8±0.2分钟-1）。肾病VLDL同样富含三酰甘油和胆固醇且磷脂含量低，但根据区带超速离心模式，其直径分布范围大且包含一个致密部分，提示存在可更快清除的中间密度脂蛋白（IDL）样颗粒。当肾病大鼠接受正常颗粒时，出现明显的清除延迟，这与血浆三酰甘油升高程度平行。在中度和重度肾病大鼠中，乳糜微粒的半衰期分别为8.3±1.4和15.2±2.5分钟-1，VLDL的半衰期相应为11.72±2.1和37.8±7.1分钟-1。正常或肾病受体的脂肪组织和肌肉对乳糜微粒三酰甘油的摄取均减少，而进入肺、肾和脾的量有所增加。VLDL三酰甘油的组织分布模式与乳糜微粒相似，只是肝脏摄取了约90%的标记物。富含脂蛋白脂肪酶的组织对三酰甘油摄取比例低表明该酶的活性不太可能限制清除速率。中度肾病大鼠脂肪组织和心脏中的脂蛋白脂肪酶活性略有降低，重度肾病大鼠中仅下降约35%。这些结果表明，肾病中的清除缺陷似乎部分归因于富含三酰甘油颗粒组成的变化，损害了它们对脂解的可及性，部分归因于其数量过多，使脂解能力饱和。
