Hofmann A F
Minerva Med. 1977 Sep 19;68(43):3011-7.
The enterohepatic circulation of bile acids in man is reviewed. The chemistry of biliary bile acids is summarized and related to the formation of primary bile acids in the liver and secondary bile acids in the intestinal lumen. New findings showing that lithocholic acid is absorbed in man are presented, and the recent experiments showing that lithocholic acid is extensively sulfated are reviewed. The consistent hepatotoxicity of chenodeoxycholic acid in the rhesus monkey, which contrasts with its non-toxicity in man, is explained by the inability of the rhesus monkey to sulfate abosrbed lithocholic acid; this accumulates in the enterohepatic circulation of the monkey causing liver damage. In man, absorbed lithocholic acid is rapidly sulfated, and the sulfated conjugates are excreted fecally without enterohepatic cycling. The physical chemistry of bile is highlighted, and it is shown that the saturation of bile with cholesterol depends on the amount of bile acids passing through the liver: at low bile acid flow rates, such as occurs during overnight fasting, bile is supersaturated in both gallstone and healthy persons. Chenodeoxycholic acid decreases cholesterol secretion into bile, renders bile unsaturated during most of the day and night, and thus induces gallstone dissolution.
本文综述了人体内胆汁酸的肠肝循环。总结了胆汁中胆汁酸的化学性质,并将其与肝脏中初级胆汁酸和肠腔内次级胆汁酸的形成相关联。介绍了新的研究结果,表明石胆酸在人体内可被吸收,并综述了近期关于石胆酸被广泛硫酸化的实验。恒河猴体内鹅去氧胆酸持续表现出肝毒性,这与其在人体内的无毒特性形成对比,原因是恒河猴无法将吸收的石胆酸硫酸化;石胆酸在猴的肠肝循环中蓄积,从而导致肝损伤。在人体内,吸收的石胆酸会迅速硫酸化,硫酸化结合物随粪便排出,不参与肠肝循环。强调了胆汁的物理化学性质,结果表明胆汁中胆固醇的饱和度取决于流经肝脏的胆汁酸量:在低胆汁酸流速情况下,如夜间禁食时,无论是胆结石患者还是健康人,胆汁都会过饱和。鹅去氧胆酸可减少胆固醇分泌入胆汁,使胆汁在白天和夜间的大部分时间内不饱和,从而促使胆结石溶解。