Gascon-Barré M, Gamache M
Centre de Recherche Clinique André-Viallet, Hôpital Saint-Luc, Montreal, Quebec, Canada.
Endocrinology. 1991 Nov;129(5):2335-44. doi: 10.1210/endo-129-5-2335.
The role of the biliary pathway in the homeostasis of the vitamin D3 (D3) group of compounds is poorly understood. The purpose of the studies was to investigate the biliary excretion pattern of materials derived from the parent compound D3 and from the hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) during constant iv infusion, and to probe the influence of 1,25(OH)2D3 pretreatment on the excretion into the bile of D3-derived materials. Under anesthesia, the bile duct, duodenum (for bile replacement), and jugular veins were cannulated. The experiments were then carried out in fully awake rats with access to food and water ad libitum during a period of 6 h. Data indicate that before steady state was reached, biliary excretion of 1,25(OH)2[3H]D3 was much more important than that of [14C]D3 with bile/plasma concentration ratios above 1 in 1,25(OH)2[3H]D3-infused animals from the 15th-60th min of infusion compared to ratios between 0.12-0.40 in [14C]D3-infused rats (P less than 0.0001); this led to a cumulative excretion 6.3-fold higher after 1,25(OH)2[3H]D3 than after [14C]D3 administration, with 3.9 +/- 0.4% and 0.6 +/- 0.1% of the dose being recovered into the bile during the first hour of excretion. However, once stable plasma concentrations were reached, the rate of excretion of the two compounds became similar, with bile/plasma concentration ratios of 0.64 +/- 0.02 and 0.70 +/- 0.02 (P greater than 0.05), and plasma bile clearance of 26.4 +/- 1.0 and 25.7 +/- 1.7 microliters/min.kg for 1,25(OH)2[3H]D3 and [14C]D3, respectively (P greater than 0.05). During that period, the MCR of 1,25(OH)2D3 was estimated to be 118.3 +/- 10.5 microliters/min.kg. On the other hand, 1,25(OH)2D3 pretreatment as constant ip infusion (14 pmol/24 h for 6 days) significantly increased bile flow [1,25(OH)2D3 treated, 44.9 +/- 1.6 microliters/min.kg; untreated, 36.6 +/- 0.5 microliters/min.kg, P less than 0.01)], leading to significant increases in the plasma bile clearance of [14C]D3-derived compounds early in the course of the study (P less than 0.004) in the presence of similar bile/plasma concentration ratios in the two groups. During the steady state phase of investigation, however, bile/plasma concentration ratios became lower in 1,25(OH)2D3-than in placebo-treated animals (P less than 0.05), but due to the 1,25(OH)2D3-mediated increase in bile flow, similar plasma bile clearances were observed in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)
胆汁途径在维生素D3（D3）类化合物体内稳态中的作用目前了解甚少。本研究的目的是在持续静脉输注期间，研究母体化合物D3和激素1,25 - 二羟基维生素D3（1,25(OH)2D3）衍生物质的胆汁排泄模式，并探究1,25(OH)2D3预处理对D3衍生物质胆汁排泄的影响。在麻醉状态下，将胆管、十二指肠（用于胆汁置换）和颈静脉插管。然后在完全清醒的大鼠中进行实验，实验期间大鼠可随意进食和饮水，持续6小时。数据表明，在达到稳态之前，1,25(OH)2[3H]D3的胆汁排泄比[14C]D3更为重要，在输注1,25(OH)2[3H]D3的动物中，从输注第15至60分钟起，胆汁/血浆浓度比高于1，而在输注[14C]D3的大鼠中该比值在0.12 - 0.40之间（P < 0.0001）；这导致1,25(OH)2[3H]D3给药后累积排泄量比[14C]D3高6.3倍，在排泄的第一小时内，分别有3.9±0.4%和0.6±0.1%的剂量回收至胆汁中。然而，一旦达到稳定的血浆浓度，两种化合物的排泄速率变得相似，1,25(OH)2[3H]D3和[14C]D3的胆汁/血浆浓度比分别为0.64±0.02和0.70±0.02（P > 0.05），血浆胆汁清除率分别为26.4±1.0和25.7±1.7微升/分钟·千克（P > 0.05）。在此期间，1,25(OH)2D3的代谢清除率估计为118.3±10.5微升/分钟·千克。另一方面，1,25(OH)2D3以持续腹腔注射（14皮摩尔/24小时，共6天）进行预处理，显著增加了胆汁流量[1,25(OH)2D3处理组为44.9±1.6微升/分钟·千克；未处理组为36.6±0.5微升/分钟·千克，P < 0.01]，导致在研究早期[14C]D3衍生化合物的血浆胆汁清除率显著增加（P < 0.004），此时两组的胆汁/血浆浓度比相似。然而，在研究的稳态阶段，1,25(OH)2D3处理组的胆汁/血浆浓度比低于安慰剂处理组（P < 0.05），但由于1,25(OH)2D3介导的胆汁流量增加，两组的血浆胆汁清除率相似。（摘要截取自400字）
