Calandra S, Tarugi P, Ghisellini M, Gherardi E
Exp Mol Pathol. 1983 Dec;39(3):282-99. doi: 10.1016/0014-4800(83)90058-8.
The changes of plasma lipoproteins which occur during the development of nephrotic syndrome induced in the rat were investigated by the administration of the antineoplastic drug adriamycin. Rats received a single intravenous injection of the drug (7.5 mg/Kg) and were sacrificed 5, 10, 15, 20, 25, and 30 days after treatment. By monitoring plasma and urine albumin, four stages in the development of nephrosis were identified: (1) a prenephrotic stage, (2) a mild nephrosis with moderate albuminuria and hypoalbuminemia; (3) a severe nephrosis with massive albuminuria and severe hypoalbuminemia; and (4) a recovery stage in which plasma albumin showed the tendency to increase. Apart from a mild elevation of plasma triacylglycerols and VLDL observed as early as Day 5, no changes in plasma cholesterol and in the other lipoprotein classes were observed at the stage of mild nephrosis (Day 10). However, as the disease became more severe (Day 15-25) there was a striking increase of HDL1 (1.050-1.090 g/ml) and, above all, of HDL2 (1.090-1.210 g/ml). VLDL and LDL also increased but at a later stage. The elevation of HDL1 and HDL2 was associated with an increase of apolipoprotein A-I in plasma (fourfold increase). Moreover, the relative content of this apolipoprotein in HDL1 and HDL2 increased as the disease progressed from mild to severe, so that in severely nephrotic rats HDL1 and HDL2 contained almost exclusively A-I and C apolipoproteins. HDL enriched in apolipoprotein A-I were also found in urine of severely nephrotic animals. Since these findings are similar to those previously described in nephrotic syndrome induced by puromycin aminonucleoside (Gherardi, E., and Calandra, S. (1982). Biochim. Biophys. Acta 710, 188.) the following conclusions can be drawn: (1) the key signs of nephrotic syndrome (albuminuria and hypoalbuminemia) precede the elevation of plasma lipoproteins; (2) the pattern of nephrotic hyperlipoproteinemia evolves as a function of the severity of the disease; (3) the accumulation of HDL enriched in apolipoprotein A-I represents an early and specific feature of nephrotic hyperlipoproteinemia in the rat.
通过给予抗肿瘤药物阿霉素，研究了大鼠诱导性肾病综合征发展过程中血浆脂蛋白的变化。大鼠接受单次静脉注射该药物（7.5毫克/千克），并在治疗后5、10、15、20、25和30天处死。通过监测血浆和尿液白蛋白，确定了肾病发展的四个阶段：（1）肾病前期；（2）轻度肾病，伴有中度蛋白尿和低白蛋白血症；（3）重度肾病，伴有大量蛋白尿和严重低白蛋白血症；（4）恢复阶段，血浆白蛋白呈上升趋势。除了早在第5天观察到血浆三酰甘油和极低密度脂蛋白轻度升高外，在轻度肾病阶段（第10天）未观察到血浆胆固醇和其他脂蛋白类别的变化。然而，随着疾病变得更加严重（第15 - 25天），高密度脂蛋白1（1.050 - 1.090克/毫升），尤其是高密度脂蛋白2（1.090 - 1.210克/毫升）显著增加。极低密度脂蛋白和低密度脂蛋白也增加，但在后期。高密度脂蛋白1和高密度脂蛋白2的升高与血浆中载脂蛋白A - I的增加有关（增加了四倍）。此外，随着疾病从轻度发展到重度，该载脂蛋白在高密度脂蛋白1和高密度脂蛋白2中的相对含量增加，因此在重度肾病大鼠中，高密度脂蛋白1和高密度脂蛋白2几乎只含有A - I和C载脂蛋白。在重度肾病动物的尿液中也发现了富含载脂蛋白A - I的高密度脂蛋白。由于这些发现与先前在嘌呤霉素氨基核苷诱导的肾病综合征中描述的发现相似（Gherardi, E., and Calandra, S. (1982). Biochim. Biophys. Acta 710, 188.），可以得出以下结论：（1）肾病综合征的关键体征（蛋白尿和低白蛋白血症）先于血浆脂蛋白升高；（2）肾病性高脂血症的模式随疾病严重程度而演变；（3）富含载脂蛋白A - I的高密度脂蛋白的积累是大鼠肾病性高脂血症的早期和特异性特征。
