小鼠模型中含长链和中链甘油三酯及鱼油的静脉注射脂质乳剂的血液清除率和组织摄取情况。

Blood clearance and tissue uptake of intravenous lipid emulsions containing long-chain and medium-chain triglycerides and fish oil in a mouse model.

作者信息

Treskova E, Carpentier Y A, Ramakrishnan R, Al-Haideri M, Seo T, Deckelbaum R J

机构信息

Department of Pediatrics, Columbia University, New York 10032, USA.

出版信息

JPEN J Parenter Enteral Nutr. 1999 Sep-Oct;23(5):253-7; discussion 258-9. doi: 10.1177/0148607199023005253.

DOI:10.1177/0148607199023005253

PMID:10485437

Abstract

BACKGROUND

Increasing interest in using different triglycerides (TGs) for specific clinical applications raised the question as to how the emulsion TG composition would affect blood clearance and emulsion delivery to hepatic and extrahepatic tissues.

METHODS

Emulsions used were long-chain soy oil TG (long-chain triglyceride [LCT]), LCT/ medium-chain triglyceride (MCT; 1:1, wt/wt), LCT/MCT/C/omega-3 (5:4:1, wt/wt) and pure fish oil (omega-3 TG) labeled with non-degradable 3H-cholesteryl oleoyl ether (3H-CE) as a particle marker. Mice (C57BL/6J) were injected with four different commercial emulsions at a nonsaturating dose of 0.4 mg TG/20 to 25 g per mouse to obtain 1st order kinetics. Blood was sampled at 0.5, 2, 5, 10, 15, and 25 minutes, and the fractional catabolic rate was determined by fitting a straight line to the logarithm of the blood 3H-CE radioactivity. Retention of 3H-CE for each tissue at 25 minutes reflected organ uptake of the emulsion.

RESULTS

Blood clearance of pure omega-3 TG (10.40% +/- 0.54% pools/h; mean +/- SE) was significantly slower than that of LCT, LCT/MCT, and LCT/MCT/omega-3 emulsion (18.9 +/- 0.6 pools/h, 17.0 +/- 0.96 pools/h, 16.5 +/- 1.08 pools/h, respectively) (p < .01). Based on 3H-CE uptake, LCT, LCT/MCT, and omega-3 TG emulsions showed similar delivery to liver (39% +/- 3.9%, 46% +/- 3.6%, 34% +/- 3.2%). Liver uptake of LCT/MCT/omega-3, (23% +/- 2.2%) was less than LCT/MCT (46% +/-3.6%, p < .0001) and LCT (39% +/- 3.9%, p = .002).

CONCLUSIONS

Results indicate slow blood clearance of pure omega-3 TG emulsion from the blood compared with emulsion in which omega-3 TG was mixed with LCT and MCT. Earlier data showed that omega-3 TG are poorly hydrolyzed in extracellular media and therefore are delivered to tissues as part of the core of emulsion remnants. Thus, our data suggest that the incorporation of omega-3 TG with LCT/MCT will result in greater delivery of omega-3 fatty acids to extrahepatic tissue, which could be important in modulating immune and other responses.

摘要

背景

对于将不同甘油三酯（TGs）用于特定临床应用的兴趣日益增加，引发了关于乳剂TG组成如何影响血液清除率以及乳剂向肝组织和肝外组织递送的问题。

方法

使用的乳剂为长链大豆油TG（长链甘油三酯[LCT]）、LCT/中链甘油三酯（MCT；1:1，重量/重量）、LCT/MCT/C/ω-3（5:4:1，重量/重量）以及用不可降解的3H-胆固醇油酰醚（3H-CE）标记的纯鱼油（ω-3 TG）作为颗粒标记物。以非饱和剂量0.4 mg TG/20至25 g每只小鼠给C57BL/6J小鼠注射四种不同的市售乳剂，以获得一级动力学。在0.5、2、5、10、15和25分钟采集血液，并通过将直线拟合到血液3H-CE放射性的对数来确定分解代谢率。25分钟时每个组织中3H-CE的保留反映了乳剂的器官摄取。

结果

纯ω-3 TG的血液清除率（10.40%±0.54%池/小时；平均值±标准误）明显慢于LCT、LCT/MCT和LCT/MCT/ω-3乳剂（分别为18.9±0.6池/小时、17.0±0.96池/小时、16.5±1.08池/小时）（p<0.01）。基于3H-CE摄取，LCT、LCT/MCT和ω-3 TG乳剂向肝脏的递送相似（39%±3.9%、46%±3.6%、34%±3.2%）。LCT/MCT/ω-3对肝脏的摄取（23%±2.2%）低于LCT/MCT（46%±3.6%，p<0.0001）和LCT（39%±3.9%，p = 0.002）。

结论

结果表明，与ω-3 TG与LCT和MCT混合的乳剂相比，纯ω-3 TG乳剂从血液中的清除较慢。早期数据表明，ω-3 TG在细胞外介质中水解不良，因此作为乳剂残余物核心的一部分递送至组织。因此，我们的数据表明，将ω-3 TG与LCT/MCT结合将导致更多的ω-3脂肪酸递送至肝外组织，这在调节免疫和其他反应中可能很重要。