<原著>閉塞性黄疸時の内因性エンドトキシン血症ラットにおけるウルソデオキシコール酸静脈内投与の効果について
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Endogenous endotoxemia, which is due to the facilitated bacterial translocation from intraluminal space of the gastrointestinal tract to portal vein in spite of the absence of a focus of infection, is possibly involved in poor biliary drainage of percutaneous transhepatic cholangiodrainage (PTCD) in the case of obstructive jaundice. Ursodeoxycholic acid (UDCA) is a bile acid, which is often orally used in the treatment of cholestasis. Herein, the protective effect of intravenous administration of UDCA against endotoxemia was determined by measuring the survival rate, endotoxin concentration in portal and peripheral veins, ATP content of rat liver and serum level of TNF-α. Endogenous endotoxemia in rats with obstructive jaundice induced by simultaneous administration of E. coli endotoxin orally at the dose of 5 mg/100g body weight and lead acetate intravenously at the dose of 5mg/100g body weight following bile duct ligation for two weeks and recanaliculization thereafter according to the model of Bailey. UDCA administration at the dose of 0.05 μmol/100g body weight/min improved the survival rate significantly. In the UDCA-treated group, the endotoxin concentration in the peripheral vein was significantly lower and ATP content was significantly recovered to the normal level. Conversely, the endotoxin concentration in the portal vein and serum level of TNF-α were not different between the UDCA-treated and saline-treated control rats. To investigate the mechanism of effect of UDCA on the secretion of endotoxin into bile, fluorescein isothiocyanate (FITC) labeled lipopolysaccharide (LPS) was administered via the portal vein and its concentration in bile was measured with a spectrophotofluorometer. A significant increase in the secretion of LPS into the bile was noticed in UDCA-treated rats, suggesting that the lower concentration of LPS in the peripheral vein in UDCA-treated rats depends on the increase in secretion of LPS into the bile. These findings demonstrate that intravenous administration of UDCA protects against endotoxemia in obstructive jaundice by activating the transport pathway of endotoxin across the hepatocytes into the bile but has no effect on Kupffer cells. Therefore, UDCA treatment may be beneficial in the case of poor biliary drainage of PTCD in obstructive jaundice.
- 近畿大学の論文
- 1994-03-25
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