Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
Department of Pathology, Massachusetts General Hospital, Boston Massachusetts, USA.
JPEN J Parenter Enteral Nutr. 2018 Feb;42(2):403-411. doi: 10.1177/0148607117695249. Epub 2017 Dec 13.
Replacement of parenteral soybean oil (SO) with fish oil (FO) is an effective therapy for intestinal failure-associated liver disease (IFALD) in children. However, practitioners remain concerned about the risk of essential fatty acid deficiency (EFAD) and sometimes treat IFALD with a combination of 50% SO and 50% FO emulsions. The purpose of this study was to determine if mixing 50% SO and 50% FO emulsions would prevent hepatosteatosis in a murine model of parenteral nutrition (PN)-induced hepatosteatosis.
C57BL/6 mice were randomized to receive oral PN with parenteral saline, FO, SO, or a mixture of 50% FO and 50% SO for 19 days. Fatty acid analysis, histologic evaluation, Nonalcoholic Steatohepatitis Clinical Research Network (NSCRN) scores, and reverse-transcriptase polymerase chain reaction for key lipogenic genes were performed.
The PN + saline group was the only group with EFAD, with a serum and hepatic triene/tetraene ratio of 0.53. NSCRN scores were highest in the PN + SO group (5.5; 95% confidence interval [CI], 4.9-6.1), followed by the PN + FO/SO (4.5; 95% CI, 3.5-5.5) group, with the lowest score in the PN + FO (2.0; 95% CI, 1.1-2.9) group. Acetyl CoA carboxylase α and acetyl CoA carboxylase β expression was lower in the PN + FO group than in the PN + FO/SO or PN + SO groups.
Our data demonstrate that a mixed fat emulsion of 50% SO and 50% FO is inferior to 100% FO in reducing hepatosteatosis in this model. These data suggest that use of parenteral SO with parenteral FO, in a 1:1 ratio, may still contribute to liver injury, although it is less hepatotoxic than pure SO.
用鱼油（FO）替代大豆油（SO）是治疗儿童肠衰竭相关肝病（IFALD）的有效方法。然而，临床医生仍然担心必需脂肪酸缺乏（EFAD）的风险，有时会使用 50%SO 和 50%FO 乳剂的混合物来治疗 IFALD。本研究旨在确定在肠外营养（PN）诱导的肝脂肪变性的小鼠模型中，混合 50%SO 和 50%FO 乳剂是否可以预防肝脂肪变性。
将 C57BL/6 小鼠随机分为口服 PN 组，给予生理盐水、FO、SO 或 50%FO 和 50%SO 混合物进行 19 天的 PN。进行脂肪酸分析、组织学评估、非酒精性脂肪性肝炎临床研究网络（NSCRN）评分和关键脂肪生成基因的逆转录聚合酶链反应。
只有 PN+盐水组出现 EFAD，血清和肝三烯/四烯比为 0.53。PN+SO 组的 NSCRN 评分最高（5.5；95%置信区间 [CI]，4.9-6.1），其次是 PN+FO/SO（4.5；95%CI，3.5-5.5）组，PN+FO 组的评分最低（2.0；95%CI，1.1-2.9）。PN+FO 组乙酰辅酶 A 羧化酶α和乙酰辅酶 A 羧化酶β的表达低于 PN+FO/SO 或 PN+SO 组。
我们的数据表明，在这种模型中，50%SO 和 50%FO 的混合脂肪乳剂在减少肝脂肪变性方面不如 100%FO。这些数据表明，尽管与纯 SO 相比，1:1 比例的 SO 和 FO 联合应用的肝毒性较小，但仍可能导致肝脏损伤。
