Lorenzo-Zúñiga Vicente, Bartolí Ramón, Planas Ramón, Hofmann Alan F, Viñado Belén, Hagey Lee R, Hernández José M, Mañé Josep, Alvarez Marco A, Ausina Vicente, Gassull Miquel Angel
Departments of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
Hepatology. 2003 Mar;37(3):551-7. doi: 10.1053/jhep.2003.50116.
Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl(4)-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 +/- 6.5 vs. 53.0 +/- 3.1 microL/kg/min; mean +/- SE, P<.05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 +/- 6.29; cholylglycine, 52.72 +/- 8.9 microL/kg/min). Total ileal bacterial content was 6-fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 +/- 0.002; cholylglycine 0.101 +/- 0.007 EU/mL) compared with placebo (0.282 +/- 0.124, P <.001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients.
进行实验以测试给予结合型胆汁酸是否会减少腹水型肝硬化大鼠的细菌过度生长、细菌移位和内毒素血症。使用了一种抗去结合-去羟基化的胆酰肌氨酸和一种易发生去结合-去羟基化的甘氨胆酸。将四氯化碳诱导的肝硬化和腹水大鼠喂食胆酰肌氨酸、甘氨胆酸（均为70毫克/千克/天）或安慰剂，持续2周。作为对照，对健康大鼠进行类似处理。在接受安慰剂的肝硬化大鼠中，急性胆瘘的胆汁分泌低于健康大鼠（27.2±6.5对53.0±3.1微升/千克/分钟；平均值±标准误，P<0.05）。给肝硬化大鼠给予结合型胆汁酸可使胆汁分泌恢复正常（胆酰肌氨酸，51.8±6.29；甘氨胆酸，52.72±8.9微升/千克/分钟）。腹水型肝硬化大鼠的回肠总细菌含量比健康大鼠高6倍。给予结合型胆汁酸可将细菌含量降至正常水平。接受结合型胆汁酸的肝硬化动物（胆酰肌氨酸，33%；甘氨胆酸，26%）的细菌移位比接受安慰剂的动物（66%）少。与安慰剂（0.282±0.124，P<0.001）相比，喂食结合型胆汁酸可降低肝硬化大鼠的内毒素血症（胆酰肌氨酸，0.098±0.002；甘氨胆酸0.101±0.007 EU/毫升）。接受结合型胆汁酸的动物（胆酰肌氨酸，10/15；甘氨胆酸，11/15；安慰剂，5/15）的存活率更高。总之，给腹水型肝硬化大鼠给予结合型胆汁酸可增加胆汁酸分泌，消除肠道细菌过度生长，减少细菌移位，降低内毒素血症，并提高存活率。口服结合型胆汁酸可能有助于预防肝硬化患者的细菌移位、内毒素血症和自发性细菌性腹膜炎。
