Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis.
Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis.
复制标题
大鼠肝脏脂蛋白分泌及对实验性肾病的影响。
DOI：
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发表时间：
1979
影响因子：
15.9
通讯作者：
C. Sparks
中科院分区：
文献类型：
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作者：
J. Marsh;C. Sparks
正常和肾病大鼠的肝脏灌注的非再循环技术。于注射嘌呤霉素后第7天观察肾脏病变情况。通过琼脂糖柱层析或连续密度超离心从灌注介质中分离氨基酸标记的脂蛋白（d < 1.21）。在这两组动物中，除了极低密度脂蛋白和新生高密度脂蛋白外，柱层析显示存在2-3 × 10（6）道尔顿的峰。该峰含有对应于<1.006、1.006 < d < 1.02和1.02 < d < 1.06的密度的脂蛋白，这表明大鼠肝脏分泌富含磷脂酰肌醇的脂蛋白的异质混合物。测量这些脂蛋白密度类别的量，并测定其脂质和载脂蛋白组成及其载脂蛋白比活性。在两组大鼠中，随着隔离密度从1.006增加到1.06，磷脂含量逐渐升高，甘油三酯含量逐渐降低。肾病患者的脂蛋白中胆固醇含量更高。在前20分钟内，肾病大鼠的肝脏分泌的所有密度等级的脂蛋白是对照组的2至3倍，但在接下来的40分钟内，与对照组相比，只有1.02 < d < 1.06和新生高密度脂蛋白保持在这个高水平。一个更大的总肝池的载脂蛋白在肾病肝推断其较低的比活性在第一个20分钟。载脂蛋白组成的肝灌注脂蛋白从肾病不同于对照组。在所有密度等级中，低分子量载脂蛋白的量降低40%，在富含谷胱甘肽的组分中，载脂蛋白B和载脂蛋白E相应增加。新生HDL中的apo A-1含量从对照组的16%增加到肾病患者的52%，apo C和apo E相应降低。当这些结果与个别载脂蛋白的比活性测量和总蛋白的净分泌速率在每个脂蛋白类相结合，它是可能的估计每一个载脂蛋白分泌的总量和标记的氨基酸的总掺入到每个。掺入标记得到的结果类似于通过直接测量脱辅基蛋白的量得到的结果。载脂蛋白E的分泌增加了1.8倍，载脂蛋白B增加了2.8倍，载脂蛋白A-1增加了8.4倍，而载脂蛋白C的分泌没有显著改变。我们解释这些结果的假设，主要刺激肝血浆蛋白合成反应蛋白尿是一般的，随后的负反馈调节影响个人载脂蛋白的合成率。这一假说的一个推论是，载脂蛋白的生物合成和分泌可能受到调节，独立于脂蛋白密度类，它是发现。
Livers from normal and nephrotic rats were perfused by the nonrecirculating technique. Nephrosis was studied on the 7th d after the injection of puromycin animonucleoside. Amino acid-labeled lipoproteins (d < 1.21) were isolated from the perfusion medium by agarose column chromatography or by sequential density ultracentrifugation. In both groups of animals, in addition to very low density lipoproteins and nascent high density lipoproteins, column chromatography revealed the presence of a peak of 2-3 x 10(6) daltons. This peak contained lipoproteins of densities corresponding to <1.006, 1.006 < d < 1.02, and 1.02 < d < 1.06, which indicated that rat liver secretes a heterogeneous mixture of triglyceride-rich lipoproteins. The amount of these lipoprotein density classes was measured and their lipid and apoprotein composition and their apoprotein specific activity were determined. In both groups of rats there was a progressive rise in phospholipid and decrease in triglyceride content as the isolation density increased from 1.006 and 1.06. The lipoproteins from the nephrotics had higher amounts of cholesterol. The livers from the nephrotic rats secreted two to three times as much lipoprotein as controls in all density classes in the first 20 min, but during the next 40 min only the 1.02 < d < 1.06 and nascent high density lipoproteins remained at this high level compared to controls. A larger total liver pool of apolipoproteins in nephrotic livers was inferred from their lower specific activities during the first 20 min. The apoprotein composition of liver perfusate lipoproteins from nephrotics differed from controls. There was a 40% decrease in the amount of low molecular weight apoproteins in all density classes, with corresponding increases in apo B and apo E in the triglyceride-rich fractions. The apo A-1 content of nascent HDL was increased from 16% in controls to 52% in nephrotics, with corresponding decreases in apo C and apo E. When these results were combined with specific activity measurements of the individual apoproteins and the net secretion rate of total protein in each lipoprotein class, it was possible to estimate the total amount of each apoprotein secreted and the total incorporation of labeled amino acids into each. The incorporation of label gave results similar to those obtained by direct measurement of the amounts of apoproteins. Apo E secretion was increased by a factor of 1.8, apo B by 2.8, and apo A-1 by 8.4, whereas the secretion of apo C was not significantly altered. We explain these results by postulating that the primary stimulus to hepatic plasma protein synthesis in response to proteinuria is general and that subsequent negative feedback regulation affects individual apolipoprotein synthesis rates. A corollary of this hypothesis is that the biosynthesis and secretion of an apoprotein may be regulated independently of the lipoprotein density class in which it is found.