Hillebrant C-G, Nyberg B, Gustafsson U, Sahlin S, Björkhem I, Rudling M, Einarsson C
Karoliniska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Eur J Clin Invest. 2002 Jul;32(7):528-34. doi: 10.1046/j.1365-2362.2002.01015.x.
Treatment with ursodeoxycholic acid and also, to some degree, statins reduces cholesterol saturation of bile. The present study aimed [1] to study the effects of combined treatment with ursodeoxycholic acid and pravastatin on hepatic cholesterol metabolism and [2] to evaluate if the addition of pravastatin to ursodeoxycholic acid treatment has beneficial effects on the lipid composition of gallbladder bile in gallstone patients.
Nineteen patients with cholesterol gallstones were subjected to combined treatment with ursodeoxycholic acid (500 mg bid) and pravastatin (20 mg bid) for three weeks before cholecystectomy. Eleven patients received ursodeoxycholic acid only and 20 untreated gallstone patients served as controls. Gallbladder bile was collected, and for both the patients receiving combined treatment and the controls a liver biopsy was also obtained peroperatively.
The cholesterol saturation of bile averaged 59% in the patients on combined treatment, 60% in the ursodeoxycholic acid-treated patients, and 130% in the untreated controls. In the patients receiving ursodeoxycholic acid, this bile salt constituted approximately 60% of all bile salts. The patients receiving combined treatment had reduced cholesterol synthesis, as reflected by a 45% reduction in serum lathosterol. The activity and the mRNA levels of cholesterol 7 alpha-hydroxylase and the mRNA levels for the low density lipoprotein-receptor were not significantly affected.
Pravastatin does not further reduce the cholesterol saturation of bile in gallstone patients treated with ursodeoxycholic acid, although hepatic cholesterol synthesis is inhibited. The study supports the important concept that de novo synthesized cholesterol is not particularly important for biliary cholesterol secretion in humans.
熊去氧胆酸治疗以及在一定程度上他汀类药物治疗可降低胆汁胆固醇饱和度。本研究旨在[1]探讨熊去氧胆酸与普伐他汀联合治疗对肝脏胆固醇代谢的影响，以及[2]评估在熊去氧胆酸治疗基础上加用普伐他汀对胆结石患者胆囊胆汁脂质成分是否有有益作用。
19例胆固醇结石患者在胆囊切除术前接受熊去氧胆酸（500mg，每日两次）和普伐他汀（20mg，每日两次）联合治疗三周。11例患者仅接受熊去氧胆酸治疗，20例未治疗的胆结石患者作为对照。收集胆囊胆汁，接受联合治疗的患者和对照组在手术中均进行肝活检。
联合治疗患者胆汁胆固醇饱和度平均为59%，熊去氧胆酸治疗患者为60%，未治疗对照组为130%。在接受熊去氧胆酸治疗的患者中，这种胆汁盐约占所有胆汁盐的60%。联合治疗患者的胆固醇合成减少，血清羊毛甾醇降低45%反映了这一点。胆固醇7α-羟化酶的活性和mRNA水平以及低密度脂蛋白受体的mRNA水平未受到显著影响。
在接受熊去氧胆酸治疗的胆结石患者中，普伐他汀虽可抑制肝脏胆固醇合成，但并未进一步降低胆汁胆固醇饱和度。该研究支持了一个重要概念，即从头合成的胆固醇对人体胆汁胆固醇分泌并非特别重要。
