Greve J W, Gouma D J, Buurman W A
Department of Surgery, Academic Hospital, University of Limburg, Maastricht, The Netherlands.
Hepatology. 1989 Oct;10(4):454-8. doi: 10.1002/hep.1840100409.
Endotoxins play an important role in the pathogenesis of complications of surgery in obstructive jaundice. Preoperative treatment with orally administered deoxycholic acid prevented endotoxin-related complications, such as renal malfunction. Other bile acids, however, were less effective, and the mechanism of action is not known. Endotoxin toxicity is considered to be largely mediated by tumor necrosis factor/cachectin, a cytokine release by mononucler phagocytes. Therefore, we studied the influence of different bile acids on endotoxin-induced tumor necrosis factor production by monocytes in vitro. Bile acids inhibit tumor necrosis factor production through a direct inhibitory effect on the monocytes. Deoxycholic acid was the most effective, chenodeoxycholic acid was less effective and ursodeoxycholic acid was ineffective in the concentrations used. Bile acids did not inactivate endotoxin as measured in a chromogenic Limulus amebocyte lysate assay. The therapeutic effect of bile acids in obstructive jaundice can be explained by an inhibition of endotoxin-induced tumor necrosis factor release by mononuclear phagocytes.
内毒素在梗阻性黄疸手术并发症的发病机制中起重要作用。术前口服脱氧胆酸治疗可预防内毒素相关并发症，如肾功能不全。然而，其他胆汁酸效果较差，其作用机制尚不清楚。内毒素毒性在很大程度上被认为是由肿瘤坏死因子/恶病质素介导的，这是一种由单核吞噬细胞释放的细胞因子。因此，我们在体外研究了不同胆汁酸对内毒素诱导单核细胞产生肿瘤坏死因子的影响。胆汁酸通过对单核细胞的直接抑制作用来抑制肿瘤坏死因子的产生。在所使用的浓度下，脱氧胆酸最有效，鹅去氧胆酸效果较差，熊去氧胆酸无效。在显色鲎试剂法检测中，胆汁酸不会使内毒素失活。胆汁酸在梗阻性黄疸中的治疗作用可以通过抑制单核吞噬细胞释放内毒素诱导的肿瘤坏死因子来解释。
