Cartwright C K, Ragland J B, Weidman S W, Sabesin S M
J Lipid Res. 1982 Jul;23(5):667-79.
The apoprotein and lipid composition and the morphology of lipoproteins was determined in rats with D-(+)-galactosamine (GalN) hepatitis. Single intraperitoneal injections of GalN at several dose levels and postinjection exsanguination times resulted in depressed levels of cholesteryl esters, an index of plasma lecithin:cholesterol acyltransferase (LCAT) activity, and increased levels of phospholipids, unesterified cholesterol, and triglycerides. Plasma withdrawn from rats 24 hr after injection of 1000 mg/kg GalN was most deficient in cholesteryl ester and was studied further by sequential isolation of VLDL, LDL, HDL1, HDL2, and HDL3. The increased plasma triglyceride (TG) after GalN treatment accumulated in TG-rich VLDL which contained two types of particles: a large (mean diameter 193.6 +/- 48.3 nm) and rough-edged particle, and a smooth one with a mean diameter (63.4 +/- 13.2 nm) similar to control VLDL (69.4 +/- 20.2 nm). The increased phospholiThe increased plasma triglyceride (TG) after GalN treatment accumulated in TG-rich VLDL which contained two types of particles: a large (mean diameter 193.6 +/- 48.3 nm) and rough-edged particle, and a smooth one with a mean diameter (63.4 +/- 13.2 nm) similar to control VLDL (69.4 +/- 20.2 nm). The increased phospholiThe increased plasma triglyceride (TG) after GalN treatment accumulated in TG-rich VLDL which contained two types of particles: a large (mean diameter 193.6 +/- 48.3 nm) and rough-edged particle, and a smooth one with a mean diameter (63.4 +/- 13.2 nm) similar to control VLDL (69.4 +/- 20.2 nm). The increased phospholipids and unesterified cholesterol were predominantly in LDL, HDL1, and HDL2 which were largely rouleaux of flattened vesicles. Density gradient ultracentrifugation of d greater than 1.006 g/ml lipoproteins confirmed these results. GalN hepatitis appeared to decrease the larger apoB335K subspecies and the apoC-III0 and apoC-III2 content of VLDL. However, total apoB concentration as GalN VLDL was increased 2.6-fold over control. LDL and HDL were markedly enriched in apoE. LDL apoB concentration was decreased by 41% while HDL was deficient in apoA-I, A-II and A-IV, and C. These results demonstrate association of increased plasma triglycerides with particles of grossly abnormal apoprotein composition, and the association of increased plasma phospholipids and unesterified cholesterol with apoE-rich lipoproteins during the LCAT defect produced by GalN hepatitis. These abnormal lipoproteins may represent an abnormal level of normal LCAT substrates important in the transport and esterification of plasma cholesterol.
测定了D-(+)-半乳糖胺（GalN）诱导肝炎大鼠的载脂蛋白和脂质组成以及脂蛋白形态。在几个剂量水平单次腹腔注射GalN，并在注射后不同时间点放血，结果显示胆固醇酯水平降低（血浆卵磷脂：胆固醇酰基转移酶（LCAT）活性的一个指标），而磷脂、游离胆固醇和甘油三酯水平升高。注射1000 mg/kg GalN后24小时从大鼠采集的血浆中胆固醇酯最缺乏，并通过依次分离极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）、高密度脂蛋白1（HDL1）、高密度脂蛋白2（HDL2）和高密度脂蛋白3（HDL3）进行了进一步研究。GalN处理后血浆甘油三酯（TG）升高，积聚在富含TG的VLDL中，该VLDL包含两种颗粒：一种大的（平均直径193.6±48.3 nm）且边缘粗糙的颗粒，以及一种平均直径（63.4±13.2 nm）与对照VLDL（69.4±20.2 nm）相似的光滑颗粒。增加的磷脂和游离胆固醇主要存在于LDL、HDL1和HDL2中，它们主要是扁平囊泡的缗钱状聚集物。密度大于1.006 g/ml的脂蛋白的密度梯度超速离心证实了这些结果。GalN肝炎似乎降低了VLDL中较大的载脂蛋白B335K亚类以及载脂蛋白C-III0和载脂蛋白C-III2的含量。然而，GalN VLDL的总载脂蛋白B浓度比对照增加了2.6倍。LDL和HDL中载脂蛋白E明显富集。LDL载脂蛋白B浓度降低了41%，而HDL缺乏载脂蛋白A-I、A-II和A-IV以及载脂蛋白C。这些结果表明，在GalN肝炎导致的LCAT缺陷期间，血浆甘油三酯升高与载脂蛋白组成严重异常的颗粒相关，血浆磷脂和游离胆固醇升高与富含载脂蛋白E的脂蛋白相关。这些异常脂蛋白可能代表了在血浆胆固醇转运和酯化中起重要作用的正常LCAT底物的异常水平。
