Wan Songlin, Yang Jianbo, Mamtawla Gulsudum, Zhang Li, Gao Xuejin, Wang Xinying
Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
Biomed Res Int. 2020 Mar 21;2020:9156359. doi: 10.1155/2020/9156359. eCollection 2020.
Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure, but parenteral nutrition-associated liver disease (PNALD) limits its long-term use. The present study is aimed at determining which pathways are altered most notably in a rat model of PNALD. We randomly assigned male Sprague-Dawley (SD) rats into two different groups, whereby they received either enteral nutrition (EN) or PN. Liver tissues were harvested from all rats 7 days later for metabolomic profiling. The composition of primary conjugated bile acids was altered, the synthesis of polyunsaturated fatty acids was reduced, the conversion of pyruvate to acetyl-CoA was blocked, and the synthesis of phosphatidylcholine was inhibited in rats with PNALD. Riboflavin, which is involved in the electron transfer process in the mitochondrial electron transport chain, was remarkably decreased in PNALD rats. A deficiency of polyunsaturated fatty acids, riboflavin, choline, and taurine might be involved in the progression of PNALD. The implications of these findings for the field of medicine are that supplementation with polyunsaturated fatty acids, riboflavin, choline, and taurine might have potential as therapeutic strategies for PNALD and also shed light on the mechanisms of PNALD.
肠外营养(PN)是治疗肠衰竭患者的一种挽救生命的疗法,但肠外营养相关肝病(PNALD)限制了其长期使用。本研究旨在确定在PNALD大鼠模型中哪些途径发生了最显著的改变。我们将雄性斯普拉格-道利(SD)大鼠随机分为两组,分别给予肠内营养(EN)或PN。7天后从所有大鼠身上采集肝脏组织进行代谢组学分析。PNALD大鼠的初级结合胆汁酸组成发生改变,多不饱和脂肪酸合成减少,丙酮酸向乙酰辅酶A的转化受阻,磷脂酰胆碱合成受到抑制。参与线粒体电子传递链电子传递过程的核黄素在PNALD大鼠中显著降低。多不饱和脂肪酸、核黄素、胆碱和牛磺酸的缺乏可能与PNALD的进展有关。这些发现对医学领域的意义在于,补充多不饱和脂肪酸、核黄素、胆碱和牛磺酸可能具有作为PNALD治疗策略的潜力,也为PNALD的机制提供了线索。