EFFECT OF URSODEOXYCHOLIC ACID ON THE KINETICS OF THE MAJOR HYDROPHOBIC BILE-ACIDS IN HEALTH AND IN CHRONIC CHOLESTATIC LIVER-DISEASE
EFFECT OF URSODEOXYCHOLIC ACID ON THE KINETICS OF THE MAJOR HYDROPHOBIC BILE-ACIDS IN HEALTH AND IN CHRONIC CHOLESTATIC LIVER-DISEASE
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DOI：
10.1002/hep.1840150409
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发表时间：
1992-04-01
期刊：
影响因子：
13.5
通讯作者：
PAUMGARTNER, G
中科院分区：
文献类型：
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作者：
BEUERS, U;SPENGLER, U;PAUMGARTNER, G
熊去氧胆酸在慢性淤胆性肝病中的有益作用被归因于将疏水性胆汁酸从内源性胆汁酸池中置换出来。为了验证这一假设，我们测定了四名健康志愿者和五名慢性淤胆性肝病患者(三名原发性胆汁性肝硬化症和两名原发性硬化性胆管炎)在熊脱氧胆酸(13-15 mg/kg体重/天)治疗前和治疗后1个月的池大小、部分周转率、合成/输入率和血清脱氧胆酸和鹅去氧胆酸水平。[H-2(4)]脱氧胆酸和[C-13]鹅去氧胆酸给药后，用毛细管气相色谱-同位素比值质谱仪测定血清中胆汁酸的动力学。在健康志愿者中，服用熊去氧胆酸期间，去氧胆酸池的大小减少了72%。在胆汁淤积性肝病患者中，熊去氧胆酸治疗前的脱氧胆酸池大小仅为健康志愿者的13%，且不受熊去氧胆酸治疗的影响。鹅去氧胆酸池的大小在健康志愿者和胆汁淤积性肝病患者中没有区别，熊去氧胆酸治疗也不会改变。在健康志愿者和胆汁淤积性肝病患者中，熊去氧胆酸治疗不改变脱氧胆酸和鹅去氧胆酸的合成/输入速率和血清水平。因为在我们的患者中，短期熊去氧胆酸治疗期间血清肝脏测试的改善并没有减少主要疏水性胆汁酸的池大小，我们得出结论，疏水性内源性胆汁酸的置换不是熊去氧胆酸在慢性胆汁淤积性肝病中的作用机制。
Beneficial effects of ursodeoxycholic acid in chronic cholestatic liver diseases have been attributed to displacement of hydrophobic bile acids from the endogenous bile acid pool. To test this hypothesis, we determined pool sizes, fractional turnover rates, synthesis/input rates and serum levels of deoxycholic acid and chenodeoxycholic acid before and 1 mo after the start of treatment with ursodeoxycholic acid (13 to 15 mg/kg body wt/day) in four healthy volunteers and five patients with chronic cholestatic liver diseases (three with primary biliary cirrhosis and two with primary sclerosing cholangitis). Bile acid kinetics were determined by combined capillary gas chromatography-isotope ratio mass spectrometry in serum samples after administration of [H-2(4)] deoxycholic acid and [C-13]chenodeoxycholic acid. In healthy volunteers, deoxycholic acid pool sizes decreased during administration of ursodeoxycholic acid by 72%. In patients with cholestatic liver diseases, deoxycholic acid pool sizes before ursodeoxycholic acid treatment were only 13% of those in healthy volunteers and were unaffected by ursodeoxycholic acid treatment. Chenodeoxycholic acid pool sizes were not different in healthy volunteers and in patients with cholestatic liver disease, and were not altered by ursodeoxycholic acid treatment. In both healthy volunteers and patients with cholestatic liver disease, synthesis/input rates and serum levels of deoxycholic acid and chenodeoxycholic acid were not altered by ursodeoxycholic acid treatment. Because in our patients improvement of serum liver tests during short-term ursodeoxycholic acid treatment was noted without a decrease of the pool sizes of the major hydrophobic bile acids, we conclude that displacement of hydrophobic endogenous bile acids is not the mechanism of action of ursodeoxycholic acid in chronic cholestatic liver disease.