Brites D, Rodrigues C M
Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Portugal.
J Hepatol. 1998 Nov;29(5):743-51. doi: 10.1016/s0168-8278(98)80255-9.
BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy is characterised by increased levels of serum bile acids. Ursodeoxycholic acid therapy corrects the serum bile acid profile. The aims of this study were: (i) to investigate bile acid excretion into colostrum of women with intrahepatic cholestasis of pregnancy; (ii) to compare concentrations of bile acids in serum and colostrum of non-treated and ursodeoxycholic acid-treated patients; and (iii) to clarify whether ursodeoxycholic acid is eliminated into colostrum following treatment.
Bile acids were assessed by gas chromatography and high-performance liquid chromatography in serum collected at delivery, and in colostrum obtained at 2+/-1 days after labour, from patients with intrahepatic cholestasis of pregnancy, non-treated (n=9) and treated (n=7) with ursodeoxycholic acid (14 mg/kg bw per day, for 14+/-7 days) until parturition.
The concentration of total bile acids in colostrum from patients with intrahepatic cholestasis of pregnancy was higher than in normals (23.3+/-14.8 micromol/l vs. 0.7+/-0.2 micromol/l, p<0.01) and cholic acid was a major species (19.0+/-13.1 micromol/l), reflecting the elevated concentrations in maternal serum (48.9+/-21.0 micromol/l, total bile acids; 33.9+/-16.7 micromol/l, cholic acid. Following ursodeoxycholic acid administration, total bile acids and cholic acid levels in colostrum diminished to 5.7+/-2.5 micromol/l and 3.6+/-1.5 micromol/l, respectively; the proportion of cholic acid decreased (60.6+/-8.0% vs. 76.8+/-5.0%, p<0.05). The ursodeoxycholic acid concentration in colostrum was maintained following treatment; its increased percentage (9.4+/-3.2% vs. 1.0+/-0.2%, p<0.01) was still lower than in maternal serum (20.8+/-3.6%, p<0.05). Only a small proportion (<1%) of lithocholic acid was found in colostrum following therapy.
Bile acid concentrations are elevated and cholic acid is the major species accumulating in colostrum, reflecting serum bile acid profiles in intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid therapy decreases endogenous bile acid levels in colostrum.
背景/目的：妊娠期肝内胆汁淤积症的特征是血清胆汁酸水平升高。熊去氧胆酸治疗可纠正血清胆汁酸谱。本研究的目的是：（i）调查妊娠期肝内胆汁淤积症患者初乳中的胆汁酸排泄情况；（ii）比较未治疗和接受熊去氧胆酸治疗患者血清和初乳中胆汁酸的浓度；（iii）明确治疗后熊去氧胆酸是否会排泄到初乳中。
采用气相色谱法和高效液相色谱法对分娩时采集的血清以及产后2±1天获得的初乳中的胆汁酸进行评估，这些样本来自妊娠期肝内胆汁淤积症患者，其中未治疗组（n = 9）和接受熊去氧胆酸治疗组（n = 7）[每天14 mg/kg体重，共14±7天，直至分娩]。
妊娠期肝内胆汁淤积症患者初乳中总胆汁酸浓度高于正常水平（23.3±14.8 μmol/L vs. 0.7±0.2 μmol/L，p<0.01），胆酸是主要成分（19.0±13.1 μmol/L），这反映了母体血清中胆汁酸浓度升高（总胆汁酸48.9±21.0 μmol/L；胆酸33.9±16.7 μmol/L）。给予熊去氧胆酸后，初乳中总胆汁酸和胆酸水平分别降至5.7±2.5 μmol/L和3.6±1.5 μmol/L；胆酸比例下降（60.6±8.0% vs. 76.8±5.0%，p<0.05）。治疗后初乳中熊去氧胆酸浓度得以维持；其增加的百分比（9.4±3.2% vs. 1.0±0.2%）仍低于母体血清（20.8±3.6%，p<0.05）。治疗后初乳中仅发现少量（<1%）石胆酸。
胆汁酸浓度升高，胆酸是初乳中积累的主要成分，反映了妊娠期肝内胆汁淤积症患者的血清胆汁酸谱。熊去氧胆酸治疗可降低初乳中内源性胆汁酸水平。
