Ng Kenneth, Stoll Barbara, Chacko Shaji, Saenz de Pipaon Miguel, Lauridsen Charlotte, Gray Matthew, Squires E James, Marini Juan, Zamora Irving J, Olutoye Oluyinka O, Burrin Douglas G
Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA.
JPEN J Parenter Enteral Nutr. 2016 Jul;40(5):656-71. doi: 10.1177/0148607114567900. Epub 2015 Jan 16.
Parenteral nutrition (PN) in preterm infants leads to PN-associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions.
Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs.
We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d-α-tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, β-sitosterol, campesterol, and stigmasterol).
Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low-density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7-hydroxylase and organic solute transporter-α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo (13)C-CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance-associated protein 2, were higher in ILE, OV, and PS vs IL.
α-tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.
早产儿肠外营养（PN）会导致PN相关肝病（PNALD）。PNALD与植物油中丰富但鱼油乳剂中缺乏的植物甾醇血清蓄积有关。
改变大豆油和鱼油脂肪乳剂中的植物甾醇和维生素E成分是否会影响早产仔猪PNALD的发展。
我们测量了接受14天PN的早产仔猪的PNALD标志物，这些仔猪接受的PN包含以下其中一种：（1）英脱利匹特（IL，100%大豆油），（2）英脱利匹特+维生素E（ILE，d-α-生育酚），（3）奥米加文（OV，100%鱼油），或（4）奥米加文+植物甾醇（PS，β-谷甾醇、菜油甾醇和豆甾醇）。
与IL组相比，ILE组、OV组和PS组的直接胆红素、γ-谷氨酰转移酶、血清甘油三酯、低密度脂蛋白的血清水平以及肝脏甘油三酯含量显著降低（P<.05）。ILE组、OV组和PS组与IL组相比，肝脏胆固醇7-羟化酶和有机溶质转运体-α的表达降低（P<.05），门静脉血浆FGF19升高。ILE组、OV组和PS组与IL组相比，肝脏线粒体肉碱棕榈酰转移酶1A和微粒体细胞色素P450 2E1脂肪酸氧化基因的表达更高。ILE组、OV组和PS组与IL组相比，体内（13）C-CDCA清除率以及孕烷X受体靶基因细胞色素P450 3A29和多药耐药相关蛋白2的表达更高。
奥米加文中的α-生育酚以及添加到英脱利匹特中的α-生育酚可防止早产仔猪血清和肝脏中PNALD的胆汁和血脂标志物升高。向奥米加文中添加植物甾醇未产生PNALD的证据。
