Elias E, Iqbal S, Knutton S, Hickey A, Coleman R
Eur J Clin Invest. 1983 Oct;13(5):383-90. doi: 10.1111/j.1365-2362.1983.tb00118.x.
Ethinyl oestradiol increased rat biliary permeability for 3H-inulin and 14C-sucrose, and significantly raised serum concentrations of bile acids after 3 and 7 days' treatment (P less than 0.0005) and bilirubin after 7 days (P less than 0.005) but not after 3 days. Following intravenous infusion of bromsulphthalein or phenolphthalein, ethinyl oestradiol-treated rats had elevated plasma concentrations of the three bile constituents, bromsulphthalein (P less than 0.0005 after 3 and 7 days), bromsulphthalein-glutathione conjugate (P less than 0.005 after 3 days; P less than 0.0005 after 7 days) and phenolphthalein glucuronide (P less than 0.005 after 3 days; P less than 0.0005 after 7 days), but the plasma concentration of unconjugated phenolphthalein, which was undetectable in bile, was unchanged. Similar changes followed partial biliary obstruction produced by bile cannula elevation. This pattern suggests that biliary constituents are refluxing from bile to plasma via the paracellular pathway, a concept further supported by structural changes in tight junction morphology in the oestrogen-treated rats. 'Leakiness' of canalicular tight junctions may explain the pathophysiology of oestrogen-induced cholestasis.
乙炔雌二醇增加了大鼠胆汁对³H-菊粉和¹⁴C-蔗糖的通透性，在治疗3天和7天后显著提高了血清胆汁酸浓度（P<0.0005），7天后显著提高了血清胆红素浓度（P<0.005），但3天后未出现这种情况。静脉注射溴磺酞或酚酞后，经乙炔雌二醇处理的大鼠血浆中三种胆汁成分的浓度升高，即溴磺酞（3天和7天后P<0.0005）、溴磺酞-谷胱甘肽共轭物（3天后P<0.005；7天后P<0.0005）和酚酞葡糖苷酸（3天后P<0.005；7天后P<0.0005），但胆汁中未检测到的未结合酚酞的血浆浓度未发生变化。胆管插管抬高导致部分胆管阻塞后也出现了类似变化。这种模式表明胆汁成分通过细胞旁途径从胆汁反流到血浆，雌激素处理的大鼠紧密连接形态的结构变化进一步支持了这一概念。胆小管紧密连接的“渗漏”可能解释了雌激素诱导的胆汁淤积的病理生理学。
