Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
EBioMedicine. 2018 Sep;35:133-141. doi: 10.1016/j.ebiom.2018.08.006. Epub 2018 Aug 10.
Although the pathogenesis of intestinal failure (IF)-associated liver disease (IFALD) is uncertain, IF-associated cholestasis mediated by the combination of intestinal injury and parenteral nutrition (PN) can lead to disturbed hepatocyte bile acids (BA) homeostasis and cause liver damages. We here show that neurotensin (NT; also known as NTS) concentrations were lower compared to healthy matched controls. Patients with cholestasis [56.1 ng/L (9.7-154.7) vs. 210.4 ng/L (134-400.4), p < .001] had lower serum NT concentrations than others. In patients' ileum, the levels of NT mRNA were positively correlated with the apical sodium dependent bile acid transporter (ASBT) mRNA levels. In mice and in cultured intestinal cells, NT treatments stimulated the expression of ASBT and led to increase BA uptake via NT receptors (NTR1 and NTR3; also known as NTSR1and NTSR3). In conclusion, these findings directly link NT with BA homeostasis, which provide an insight into the complex mechanisms mediating the development of liver disease in pediatric patients with IF.
尽管肠衰竭（IF）相关肝病（IFALD）的发病机制尚不清楚，但肠损伤和肠外营养（PN）联合介导的 IF 相关胆汁淤积可导致肝细胞胆汁酸（BA）稳态紊乱，并引起肝损伤。我们在此表明，神经降压素（NT；也称为 NTS）浓度低于健康匹配对照组。与其他患者相比，发生胆汁淤积的患者 [56.1ng/L（9.7-154.7）vs. 210.4ng/L（134-400.4），p<.001] 血清 NT 浓度更低。在患者的回肠中，NT mRNA 水平与顶端钠依赖性胆汁酸转运蛋白（ASBT）mRNA 水平呈正相关。在小鼠和培养的肠细胞中，NT 处理可刺激 ASBT 的表达，并通过 NT 受体（NTR1 和 NTR3；也称为 NTSR1 和 NTSR3）导致 BA 摄取增加。总之，这些发现将 NT 与 BA 稳态直接联系起来，为理解儿科 IF 患者肝病发展的复杂机制提供了新的视角。
