一项新的研究解释了为什么医院内的静脉内输入以大豆为基础的脂质会引起肝脏疾病。这些发现为转用基于鱼油的脂质可能会降低患者肝脏损害的风险增添了证据。
基于鱼油的静脉内营养输入在欧洲是常见的，但在美国，大豆脂质仍然是标准的静脉内营养输入。肠外营养（PN）——这是一种用静脉输入来代替摄食的方法——是一种能挽救那些无法耐受管道喂食的住院病人生命的选项。各个年龄的人都可接受静脉内营养输入。不幸的是，PN会损害肝脏并会导致PN相关的肝脏疾病。肠衰竭的早产儿及儿童的风险尤其高。
曾经有人提出，与基于鱼油的脂质相比，大豆脂质的使用会增加PN相关性肝脏疾病的风险，但为什么会出现这种情况则仍然不清楚。
Karim El Kasmi使用了一种模拟在肠道损伤的婴儿中所见的PN-相关性肝脏疾病类型的小鼠模型。他们发现静脉内营养的成分之一——一种叫做豆甾醇的脂质（它源自大豆类植物）——可能促成了肝脏损伤。在肝脏中的大豆化合物的积聚会激活肝内的免疫细胞并可能会以触发疾病的方式干扰肝内的基因表达。
研究人员还指出，由肠道细菌所制造的消化产物可通过受损的肠道吸收，而这可能会加重肝脏的损伤。
这些发现表明，人们需要更多地关注给病人静脉内输入的脂质的量及类型，尤其是在那些罹患会引起肠衰减疾病的婴儿及儿童中是这样。研发新型的静脉内输入的脂质配方或转换为以鱼油为基础的脂质可能会减少医院及诊所中的PN相关性肝脏疾病的发病率。
原文摘要
Abstract
Parenteral nutrition–associated liver disease (PNALD) is a serious complication of PN in infants who do not tolerate enteral feedings, especially those with acquired or congenital intestinal diseases. Yet, the mechanisms underlying PNALD are poorly understood. It has been suggested that a component of soy oil (SO) lipid emulsions in PN solutions, such as plant sterols (phytosterols), may be responsible for PNALD, and that use of fish oil (FO)–based lipid emulsions may be protective. We used a mouse model of PNALD combining PN infusion with intestinal injury to demonstrate that SO-based PN solution causes liver damage and hepatic macrophage activation and that PN solutions that are FO-based or devoid of all lipids prevent these processes. We have furthermore demonstrated that a factor in the SO lipid emulsions, stigmasterol, promotes cholestasis, liver injury, and liver macrophage activation in this model and that this effect may be mediated through suppression of canalicular bile transporter expression (Abcb11/BSEP, Abcc2/MRP2) via antagonism of the nuclear receptors Fxr and Lxr, and failure of up-regulation of the hepatic sterol exporters (Abcg5/g8/ABCG5/8). This study provides experimental evidence that plant sterols in lipid emulsions are a major factor responsible for PNALD and that the absence or reduction of plant sterols is one of the mechanisms for hepatic protection in infants receiving FO-based PN or lipid minimization PN treatment. Modification of lipid constituents in PN solutions is thus a promising strategy to reduce incidence and severity of PNALD.
原文摘要链接
