Reichen J, Berr F, Le M, Warren G H
Am J Physiol. 1985 Jul;249(1 Pt 1):G48-57. doi: 10.1152/ajpgi.1985.249.1.G48.
To elucidate the role of calcium in regulation of canalicular bile flow, we studied biliary sucrose permeability and the transport kinetics of taurocholate in the in situ perfused rat liver. Calcium deprivation did not adversely affect viability or ultrastructural appearances of the liver. Removal of calcium led to initial choleresis followed by cholestasis dependent on external ionized calcium concentration. Biliary recovery of [14C]sucrose relative to that of tritiated water was determined by a biliary multiple-indicator dilution technique. Analysis in terms of irreversible thermodynamics suggested that biliary permeability to sucrose increased due to a change in the sieving coefficient from 0.135 to 0.435. Biliary recovery of taurocholate was significantly (P less than 0.001) reduced in low-calcium medium (from 79.6 +/- 6.5 to 17.6 +/- 11.8%). This was not due to a defect in hepatocellular uptake of taurocholate as determined in the perfused rat liver by a multiple-indicator dilution technique and in isolated hepatocytes. We conclude that calcium deprivation-induced cholestasis is characterized by an increased biliary permeability, a defect in cellular translocation and/or canalicular secretion of bile salts, and a defect in bile salt-independent bile flow.
为阐明钙在调节胆小管胆汁流动中的作用，我们研究了原位灌注大鼠肝脏中胆汁蔗糖通透性及牛磺胆酸盐的转运动力学。钙缺乏对肝脏的活力或超微结构外观并无不利影响。去除钙会导致最初的胆汁分泌增多，随后出现依赖于细胞外离子钙浓度的胆汁淤积。通过胆汁多指示剂稀释技术测定了相对于氚标记水而言，[14C]蔗糖的胆汁回收率。根据不可逆热力学分析表明，由于筛分系数从0.135变为0.435，胆汁对蔗糖的通透性增加。在低钙培养基中，牛磺胆酸盐的胆汁回收率显著降低（P小于0.001）（从79.6±6.5%降至17.6±11.8%）。通过多指示剂稀释技术在灌注大鼠肝脏及分离的肝细胞中测定发现，这并非由于肝细胞摄取牛磺胆酸盐存在缺陷所致。我们得出结论，钙缺乏诱导的胆汁淤积的特征是胆汁通透性增加、胆盐的细胞转运和/或胆小管分泌存在缺陷以及不依赖胆盐的胆汁流动存在缺陷。
