Festi Davide, Montagnani Marco, Azzaroli Francesco, Lodato Francesca, Mazzella Giuseppe, Roda Aldo, Di Biase Anna Rita, Roda Enrico, Simoni Patrizia, Colecchia Antonio
Department of Internal Medicine and Gastroenterology, Policlinico S Orsola-Malpighi, Bologna, Italy.
Curr Clin Pharmacol. 2007 May;2(2):155-77. doi: 10.2174/157488407780598171.
Ursodeoxycholic acid (UDCA), previously used for cholesterol gallstone dissolution, is currently considered the first choice therapy for many forms of cholestatic syndromes. Many mechanisms and sites of action have been proposed for UDCA, but definitive data are still missing regarding the key points of its efficacy and optimal dosage in order to achieve a sustained clinical effect. Among the suggested mechanisms of action of UDCA, changes in bile acid pool composition, hepatocyte membrane protection, immunomodulatory effects and bicarbonate-rich hypercholeresis have been extensively studied. However, recent evidence indicate that UDCA is a potent intracellular signalling agent that counterbalances impaired biliary secretion, inhibits hepatocyte apoptosis and protects injured cholangiocytes against toxic effects of bile acids. It is clear that the relative contribution of these mechanisms to the anticholestatic action of UDCA depends on the type and stage of the liver injury. Available clinical evidence suggest that UDCA treatment has to be initiated as early as possible and that higher doses could be more efficacious in inducing and maintaining clinical remission of cholestatic diseases. The future availability of UDCA derivatives will possibly enhance the chances to effectively treat chronic cholestatic diseases.
熊去氧胆酸（UDCA）曾用于溶解胆固醇性胆结石，目前被认为是多种胆汁淤积综合征的首选治疗药物。关于UDCA的作用机制和作用位点已提出多种，但在其疗效关键点及实现持续临床效果的最佳剂量方面，仍缺乏确切数据。在UDCA的作用机制中，胆汁酸池组成变化、肝细胞膜保护、免疫调节作用以及富含碳酸氢盐的胆汁分泌增多等方面已得到广泛研究。然而，最近的证据表明，UDCA是一种有效的细胞内信号传导剂，可抵消胆汁分泌受损、抑制肝细胞凋亡并保护受损胆管细胞免受胆汁酸的毒性作用。显然，这些机制对UDCA抗胆汁淤积作用的相对贡献取决于肝损伤的类型和阶段。现有临床证据表明，UDCA治疗必须尽早开始，且较高剂量在诱导和维持胆汁淤积性疾病的临床缓解方面可能更有效。UDCA衍生物的未来可用性可能会增加有效治疗慢性胆汁淤积性疾病的机会。
