Serrano M A, Brites D, Larena M G, Monte M J, Bravo M P, Oliveira N, Marin J J
Department of Biochemistry and Molecular Biology, University of Salamanca, Spain.
J Hepatol. 1998 May;28(5):829-39. doi: 10.1016/s0168-8278(98)80234-1.
BACKGROUND/AIMS: The existence of impairment in bile acid transport across the placenta during intrahepatic cholestasis of pregnancy and the effect of ursodeoxycholic acid treatment (1 g/day) were investigated.
Kinetic parameters were calculated from experiments carried out on membrane vesicles obtained from basal (TPMb, fetal-facing) and apical (TPMa, maternal-facing) trophoblast plasma membranes. Bile acid uptake was measured using varying concentrations of [14C]-glycocholate and a rapid filtration technique.
The maximal velocity of transport (Vmax), the apparent affinity constant (Kt) and the efficiency (Ef) of transport (Vmax/Kt) of the anion:bile acid exchanger located at the TPMb were reduced in intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid induced a reversal of Vmax, Kt and Ef to normal values. Owing to the 3-fold increase in Vmax, with no change in Kt, intrahepatic cholestasis of pregnancy induced an enhancement in Ef of ATP-independent bile acid transport across TPMa. Both Vmax and Ef were restored to normal values by ursodeoxycholic acid. Finally, in ATP-dependent bile acid transport across TPMa, a reduction in the Ef due to an increase in Vmax together with a more pronounced increase in Kt was found. This impairment was also reversed by ursodeoxycholic acid.
These results suggest that placenta bile acid transport systems are impaired in intrahepatic cholestasis of pregnancy. Moreover, together with the confirmed beneficial effect for intrahepatic cholestasis of pregnancy patients, such as the relief of pruritus and the improvement in biochemical markers of cholestasis, ursodeoxycholic acid treatment restores the ability of the placenta to carry out vectorial bile acid transfer.
背景/目的：研究妊娠肝内胆汁淤积症时胆汁酸跨胎盘转运的损伤情况以及熊去氧胆酸治疗（每日1克）的效果。
通过对从基底（TPMb，面向胎儿）和顶端（TPMa，面向母体）滋养层质膜获得的膜囊泡进行实验来计算动力学参数。使用不同浓度的[14C] - 甘氨胆酸盐和快速过滤技术测量胆汁酸摄取。
妊娠肝内胆汁淤积症时，位于TPMb的阴离子：胆汁酸交换器的最大转运速度（Vmax）、表观亲和常数（Kt）和转运效率（Ef，Vmax / Kt）降低。熊去氧胆酸使Vmax、Kt和Ef恢复到正常水平。由于Vmax增加了3倍，而Kt不变，妊娠肝内胆汁淤积症导致跨TPMa的非ATP依赖性胆汁酸转运的Ef增强。熊去氧胆酸使Vmax和Ef均恢复到正常水平。最后，在跨TPMa的ATP依赖性胆汁酸转运中，发现由于Vmax增加以及Kt更显著增加导致Ef降低。这种损伤也被熊去氧胆酸逆转。
这些结果表明，妊娠肝内胆汁淤积症时胎盘胆汁酸转运系统受损。此外，与已证实的对妊娠肝内胆汁淤积症患者的有益作用（如瘙痒缓解和胆汁淤积生化指标改善）一起，熊去氧胆酸治疗可恢复胎盘进行矢量胆汁酸转运的能力。
