Yang Runkuan, Zhu Shengtao, Pischke Soeren Erik, Haugaa Hakon, Zou Xiaoping, Tonnessen Tor Inge
Department of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania.
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
J Surg Res. 2018 Aug;228:14-19. doi: 10.1016/j.jss.2018.02.049. Epub 2018 Mar 21.
Obstructive jaundice (OJ) patients with cholangitis are prone to sepsis; however, the underlying mechanisms are still not clear and need to be clarified.
Analyzing all available published data related to the title of this article.
OJ leads to absence of gut luminal bile and accumulation of hepatic and circulating bile acids. Absence of gut luminal bile deprives the gut from its antiinflammatory, endotoxin-binding, bacteriostatic, mucosal-trophic, epithelial tight-junction maintaining, and gut motility-regulating effects, leading to gut bacterial overgrowth, mucosal atrophy, mucosal tight-junction loss, and gut motility dysfunction. These alterations promote intestinal endotoxin and bacterial translocation (BT) into portal and systemic circulation. Gut BT triggers systemic inflammation, which can lead to multiple organ dysfunctions in OJ. The accumulation of hepatic and circulating bile acids kills/damages hepatocyte and Kupffer cells, and it also significantly decreases the number of liver natural killer T-cells in OJ. This results in impaired hepatic and systemic immune function, which facilitates BT. In addition, neutralizing bile HMGB1 can reverse endotoxemic bile-induced gut BT and mucosal injury in mice, suggesting that bile HMGB1 in OJ patients can be responsible for internal drainage-related clinical complications. Moreover, the elevated circulating HMGB1 level may contribute to multiple organ injuries, and it might also mediate gut BT in OJ.
HMGB1 may significantly contribute to systemic inflammation and multiple organ dysfunctions in OJ.
患有胆管炎的梗阻性黄疸（OJ）患者易发生败血症；然而，其潜在机制仍不清楚，需要阐明。
分析与本文标题相关的所有已发表的可用数据。
OJ导致肠腔内胆汁缺乏以及肝脏和循环胆汁酸的蓄积。肠腔内胆汁缺乏使肠道失去其抗炎、内毒素结合、抑菌、黏膜营养、维持上皮紧密连接以及调节肠道运动的作用，导致肠道细菌过度生长、黏膜萎缩、黏膜紧密连接丧失以及肠道运动功能障碍。这些改变促进肠道内毒素和细菌易位（BT）进入门静脉和体循环。肠道BT引发全身炎症，这可导致OJ患者出现多器官功能障碍。肝脏和循环胆汁酸的蓄积会杀死/损伤肝细胞和库普弗细胞，并且还会显著减少OJ患者肝脏自然杀伤T细胞的数量。这导致肝脏和全身免疫功能受损，从而促进BT。此外，中和胆汁中的高迁移率族蛋白B1（HMGB1）可逆转内毒素血症胆汁诱导的小鼠肠道BT和黏膜损伤，这表明OJ患者胆汁中的HMGB1可能是导致内引流相关临床并发症的原因。此外，循环中升高的HMGB1水平可能导致多器官损伤，并且它也可能介导OJ中的肠道BT。
HMGB1可能在很大程度上导致OJ中的全身炎症和多器官功能障碍。
