Buscher H P, Meder I, MacNelly S, Gerok W
Medizinische Klinik, Universität Freiburg, Germany.
Hepatology. 1993 Mar;17(3):494-9.
The liver has a great reserve capacity for hepatobiliary bile salt transport. This study was performed to elucidate the significance of this capacity in ethinyl estradiol-induced cholestasis by direct visualization of the zonal involvement in taurocholate transport. The acinar distribution of [3H]taurocholate was determined by histoautoradiographical study of cryopreserved liver slices in normal rats and rats treated with ethinyl estradiol for 5 days. Silver grain densities over the different acinar zones were estimated on digitized image analysis. In control animals, histoautoradiographical study performed 4 min after the start of perfusion showed restriction of taurocholate to acinar zone 1. In contrast, in ethinyl estradiol-treated animals, taurocholate was also found in zone 2 and, in smaller concentrations, in zone 3. In control animals, the relative blackenings by silver grains of acinar zones 1, 2 and 3 were 66% +/- 1.2%, 25% +/- 1.6% and 5% +/- 0.6%, respectively. After 5 days of ethinyl estradiol treatment, blackenings were 58% +/- 1.5%, 36% +/- 2.1% and 12% +/- 0.8%, respectively. As early as 15 sec after injection of [3H]taurocholate, the bile canalicular areas of the cell plates and the bile ductules of ethinyl estradiol-treated animals were labeled as intensely as those of control animals. Our results demonstrate ethinyl estradiol-induced recruitment of the acinar zones 2 and 3 for hepatobiliary taurocholate transport. This recruitment may largely compensate for reduction of transport capacity of periportal hepatocytes in early cholestasis.
肝脏在肝胆胆汁盐转运方面具有很大的储备能力。本研究旨在通过直接观察牛磺胆酸盐转运的区域参与情况，阐明这种能力在乙炔雌二醇诱导的胆汁淤积中的意义。通过对正常大鼠和经乙炔雌二醇处理5天的大鼠的冷冻肝脏切片进行组织放射自显影研究，确定[3H]牛磺胆酸盐的腺泡分布。在数字化图像分析中估计不同腺泡区域上的银粒密度。在对照动物中，灌注开始后4分钟进行的组织放射自显影研究显示牛磺胆酸盐局限于腺泡1区。相比之下，在经乙炔雌二醇处理的动物中，在2区也发现了牛磺胆酸盐，在3区的浓度较低。在对照动物中，腺泡1区、2区和3区银粒的相对黑化程度分别为66%±1.2%、25%±1.6%和5%±0.6%。经乙炔雌二醇处理5天后，黑化程度分别为58%±1.5%、36%±2.1%和12%±0.8%。早在注射[3H]牛磺胆酸盐后15秒，经乙炔雌二醇处理的动物的细胞板胆小管区域和胆小管就与对照动物的一样被强烈标记。我们的结果表明，乙炔雌二醇诱导腺泡2区和3区参与肝胆牛磺胆酸盐转运。这种参与可能在很大程度上补偿早期胆汁淤积时门静脉周围肝细胞转运能力的降低。
