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一种仅含中链和鱼油甘油三酯的静脉注射用脂质乳剂的体内和体外性质。

In vivo and in vitro properties of an intravenous lipid emulsion containing only medium chain and fish oil triglycerides.

作者信息

Ton Mimi N, Chang Chuchun, Carpentier Yvon A, Deckelbaum Richard J

机构信息

Division of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.

出版信息

Clin Nutr. 2005 Aug;24(4):492-501. doi: 10.1016/j.clnu.2005.03.001. Epub 2005 Apr 9.

Abstract

BACKGROUND & AIMS: The triglyceride (TG) fatty acyl composition in lipid emulsions influences their metabolism. Little is known about the effects of long chain omega-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between omega-3 containing emulsions in their metabolism and tissue-targeting in vivo in a mouse model, and in vitro using lipolysis and cell culture experiments.

METHODS

Soy oil (LCT), MCT/LCT/omega-3 (5:4:1, wt/wt/wt), and MCT/omega-3 (8:2, wt/wt) emulsions were radiolabeled with nondegradable 1alpha,2alpha (n)-[3H] cholesteryl oleoyl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection. Blood samples obtained over 25 min and extracted organs were used to measure the tissue distribution of lipid emulsion particles. Lipoprotein lipase (LpL)-mediated hydrolysis experiments and cell uptake studies in cultured J774 murine macrophages were also performed.

RESULTS

Blood clearance of 8:2 was 13.4% and 29.8% faster compared to 5:4:1 and LCT, respectively. LCT had greatest liver uptake. LpL-mediated hydrolysis was greatest in 8:2 and lowest in LCT. Overall, cell TG accumulation in the presence of apolipoprotein E was least with 8:2.

CONCLUSIONS

Our data shows that 8:2 had the most efficient blood clearance but less hepatic uptake in vivo. In vitro, 8:2 had both highest hydrolysis by LpL and intracellular TG utilization in the presence of apoE. Thus, an 8:2 lipid emulsion undergoes efficient blood clearance and may direct omega-3 PUFA more towards extrahepatic tissues.

摘要

背景与目的

脂质乳剂中的甘油三酯(TG)脂肪酸组成会影响其代谢。关于长链ω-3多不饱和脂肪酸(PUFA)对脂质乳剂代谢的影响知之甚少。我们在小鼠模型中研究了含ω-3的乳剂在体内代谢和组织靶向方面的可能差异,并通过体外脂解和细胞培养实验进行了研究。

方法

用不可降解的1α,2α(n)-[3H]胆固醇油酰醚对大豆油(LCT)、中链甘油三酯/长链甘油三酯/ω-3(5:4:1,重量/重量/重量)和中链甘油三酯/ω-3(8:2,重量/重量)乳剂进行放射性标记,以追踪单次注射后C57BL/6J小鼠体内核心颗粒的代谢。在25分钟内采集的血样和提取的器官用于测量脂质乳剂颗粒的组织分布。还进行了脂蛋白脂肪酶(LpL)介导的水解实验以及在培养的J774小鼠巨噬细胞中的细胞摄取研究。

结果

与5:4:1和LCT相比,8:2的血液清除率分别快13.4%和29.8%。LCT在肝脏中的摄取量最大。LpL介导的水解在8:2中最大,在LCT中最低。总体而言,在载脂蛋白E存在的情况下,8:2导致的细胞TG积累最少。

结论

我们的数据表明,8:2具有最有效的血液清除率,但在体内肝脏摄取较少。在体外,8:2在载脂蛋白E存在的情况下,LpL水解率最高且细胞内TG利用率最高。因此,8:2脂质乳剂具有高效的血液清除率,并且可能使ω-3 PUFA更多地导向肝外组织。

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