Handa T, Eguchi Y, Miyajima K
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Pharm Res. 1994 Sep;11(9):1283-7. doi: 10.1023/a:1018990327466.
Emulsions composed of soy bean triglyceride (TG), egg yolk phosphatidylcholine (PC), cholesterol (Chol) or cholesteryl-oleate (CO), labeled with a cholesteryl ether (3H-CHE) and a triglyceride (14C-TO), were injected into rats. 14C-TO was removed from plasma faster than 3H-CHE. The 14C-labeled moiety is cleaved by digestion of the TG in the emulsion in plasma and is removed to the endothelial cells (lipolysis). In contrast, the 3H-label remains stably associated and represents circulating emulsion particles. The majority (90%) of the 3H-label disappearing from the plasma accumulated in the liver for all types of emulsions. On the basis of these observations, the lipolysis and the removal of emulsion particles to organs (mainly liver) were determined: 30 mole percent of cholesterol (Chol) at the TG-PC emulsion surface markedly retarded organ uptake, but the effect on lipolysis was rather small; 20 mole percent of cholesteryl oleate (CO) in the TG-PC emulsion cores delayed both organ uptake and lipolysis, and induced a rapid increase in organ uptake rate after the initial delay accompanying the gradual progress of lipolysis. Lipolysis led to the enrichment of the cores with CO. Replacement of the core TG by CO, however, induced strong suppression of the liver uptake. These results show that the lipid composition at both surface and core of emulsion particles is a crucial factor in metabolism in the rat.
将由大豆甘油三酯(TG)、蛋黄磷脂酰胆碱(PC)、胆固醇(Chol)或胆固醇油酸酯(CO)组成,并标记有胆固醇醚(3H-CHE)和甘油三酯(14C-TO)的乳剂注射到大鼠体内。14C-TO从血浆中清除的速度比3H-CHE快。14C标记部分在血浆中通过乳剂中TG的消化而裂解,并被转运至内皮细胞(脂解作用)。相比之下,3H标记保持稳定结合,并代表循环中的乳剂颗粒。对于所有类型的乳剂,从血浆中消失的3H标记的大部分(90%)积聚在肝脏中。基于这些观察结果,确定了乳剂颗粒的脂解作用以及向器官(主要是肝脏)的清除情况:TG-PC乳剂表面30摩尔百分比的胆固醇(Chol)显著延迟了器官摄取,但对脂解作用的影响相当小;TG-PC乳剂核心中20摩尔百分比的胆固醇油酸酯(CO)延迟了器官摄取和脂解作用,并在伴随脂解作用逐渐进展的初始延迟后导致器官摄取速率迅速增加。脂解作用导致核心中CO富集。然而,用CO替代核心TG会强烈抑制肝脏摄取。这些结果表明,乳剂颗粒表面和核心的脂质组成是大鼠代谢中的关键因素。