Garber D W, Gottlieb B A, Marsh J B, Sparks C E
J Clin Invest. 1984 Oct;74(4):1375-83. doi: 10.1172/JCI111548.
The effects of experimental nephrosis in rats, produced by puromycin aminonucleoside, include an elevation of plasma levels of all lipoprotein density classes and the appearance of high density lipoprotein (HDL) rich in apoprotein (apo) A-I and deficient in apo A-IV and apo E. The hyperlipoproteinemia is associated with an increase in hepatic synthesis of lipoproteins. The possible role of decreased very low density lipoprotein (VLDL were obtained from nonfasting animals by ultracentrifugation at d 1.006 and included chylomicrons) catabolism and its relationship to the apolipoprotein composition of nephrotic high density lipoproteins (1.063 less than d less than 1.210, or 1.072 less than d less than 1.210 [HDL]) was explored. When 125I-VLDL was injected, the faster plasma clearance of lower molecular weight apolipoprotein B (apo BL) compared with that of higher molecular weight apo BH which is seen in normal rats was not observed in nephrotic rats. Less labeled phospholipid, apo C, and apo E were transferred from VLDL to higher lipoprotein density classes. Heparin-releasable plasma lipoprotein lipase and hepatic lipase activities were decreased by 50% in nephrotic rats compared with pair-fed controls. Perfusion of livers with medium that contained heparin released 50% less lipase activity in nephrotic rats than in controls. When heparin was injected intravenously, significant decreases in plasma levels of triglycerides and significant increases in levels of free fatty acids were observed in both groups of animals. In the nephrotic rats, 86% of the free fatty acids were in the lipoprotein fractions, as compared with 16% in the controls. Heparin treatment did not restore to normal the decreased apo BL clearance in nephrotic rats but it produced an increased amount of apo A-IV and apo E in the plasma HDL. In vitro addition of partially pure lipoprotein lipase to whole serum from nephrotic rats significantly increased the content of apo E in HDL. We conclude that the abnormal apoprotein composition of HDL in experimental nephrosis is the result of altered entry of apolipoproteins from triglyceride-rich lipoproteins, probably because of decreased lipolysis.
嘌呤霉素氨基核苷诱导的大鼠实验性肾病的影响包括所有脂蛋白密度类别的血浆水平升高，以及出现富含载脂蛋白（apo）A-I、缺乏apo A-IV和apo E的高密度脂蛋白（HDL）。高脂血症与肝脏脂蛋白合成增加有关。研究了极低密度脂蛋白（VLDL，通过在d 1.006超速离心从非禁食动物获得，包括乳糜微粒）分解代谢降低的可能作用及其与肾病性高密度脂蛋白（1.063＜d＜1.210，或1.072＜d＜1.210 [HDL]）载脂蛋白组成的关系。注射125I-VLDL后，肾病大鼠未出现正常大鼠中可见的低分子量载脂蛋白B（apo BL）与高分子量apo BH相比更快的血浆清除情况。较少的标记磷脂、apo C和apo E从VLDL转移到更高脂蛋白密度类别。与配对喂养的对照组相比，肾病大鼠中肝素可释放的血浆脂蛋白脂肪酶和肝脂肪酶活性降低了50%。用含肝素的培养基灌注肝脏时，肾病大鼠释放的脂肪酶活性比对照组少50%。静脉注射肝素后，两组动物的血浆甘油三酯水平均显著降低，游离脂肪酸水平均显著升高。在肾病大鼠中，86%的游离脂肪酸存在于脂蛋白组分中，而对照组为16%。肝素治疗未使肾病大鼠中降低的apo BL清除恢复正常，但它使血浆HDL中apo A-IV和apo E的量增加。在体外向肾病大鼠的全血清中添加部分纯化的脂蛋白脂肪酶可显著增加HDL中apo E的含量。我们得出结论，实验性肾病中HDL异常的载脂蛋白组成是富含甘油三酯脂蛋白中载脂蛋白进入改变的结果，可能是由于脂解减少。
