Smith J L, Lear S R, Forte T M, Ko W, Massimi M, Erickson S K
Department of Medicine, University of California, San Francisco, and Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
J Lipid Res. 1998 Nov;39(11):2237-49.
Origins of hyperlipidemia and cholestasis that occur during pregnancy were investigated by examining expression of key elements related to plasma and hepatic cholesterol metabolism during pregnancy, lactation, and post-lactation in the rat model. Among major findings were: during pregnancy, the activities of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, acyl coenzyme A:cholesterol acyltransferase, acyl coenzyme A:diacylglycerol acyltransferase, cholesterol 7alpha-hydroxylase, cholesterol ester hydrolases, low density lipoprotein receptors, LRP, and mdr2 were significantly lower or similar to non-pregnant controls while SR-B1 was elevated. Once lactation began, reductase, cholesterol acyltransferase, 7alpha-hydroxylase activities, low density lipoprotein receptors, and mdr2 increased while SR-B1 decreased. In later stages of lactation most hepatic elements returned to near control levels. Plasma cholesterol levels were higher than control at birth and during lactation with increase in LDL-size particles. By 24 h post-lactation, plasma triglycerides were 3.7-fold higher while cholesterol remained unchanged. Very large lipoproteins were present while LDL-size particles were now absent. Hepatic cholesterol acyltransferase had decreased to 27% of control while diacylglycerol acyltransferase increased 3-fold and low density lipoprotein receptors doubled. Most elements were normalized 3 weeks after weaning except for LRP and low density lipoprotein receptors which were elevated. These studies provide an integrated picture of expression of key elements of hepatic and plasma cholesterol metabolism during pregnancy and lactation and advance understanding of hyperlipidemia and cholestasis during these states.
通过检测大鼠模型在妊娠、哺乳及哺乳后期与血浆和肝脏胆固醇代谢相关的关键因子的表达，研究了孕期发生的高脂血症和胆汁淤积的起源。主要发现如下：在孕期，肝脏3-羟基-3-甲基戊二酰辅酶A还原酶、酰基辅酶A：胆固醇酰基转移酶、酰基辅酶A：二酰甘油酰基转移酶、胆固醇7α-羟化酶、胆固醇酯水解酶、低密度脂蛋白受体、LRP和mdr2的活性显著低于或与未孕对照组相似，而SR-B1升高。一旦开始哺乳，还原酶、胆固醇酰基转移酶、7α-羟化酶活性、低密度脂蛋白受体和mdr2增加，而SR-B1降低。在哺乳后期，大多数肝脏因子恢复到接近对照水平。出生时和哺乳期间血浆胆固醇水平高于对照组，低密度脂蛋白大小的颗粒增加。哺乳后24小时，血浆甘油三酯高出3.7倍，而胆固醇保持不变。存在非常大的脂蛋白，而低密度脂蛋白大小的颗粒此时不存在。肝脏胆固醇酰基转移酶降至对照的27%，而二酰甘油酰基转移酶增加3倍，低密度脂蛋白受体增加一倍。除了升高的LRP和低密度脂蛋白受体外，大多数因子在断奶后3周恢复正常。这些研究提供了妊娠和哺乳期间肝脏和血浆胆固醇代谢关键因子表达的综合情况，并增进了对这些状态下高脂血症和胆汁淤积的理解。
