Moslen M T, Kanz M F, Bhatia J, Smith C V, Rassin D K
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0605.
Exp Mol Pathol. 1994 Aug;61(1):1-15. doi: 10.1006/exmp.1994.1021.
We studied the effects of a transient elevation in biliary pressure on biliary glutathione and amino acids in rats. Other biliary solutes monitored were total bile salt, Pi, which is a putative marker of paracellular leakage, and glucose, which is reabsorbed from the biliary tract. Experiments were carried out on anesthetized rats intraduodenally infused with taurocholate to maintain bile flow during a 2-hr basal period, a 4-hr pressure period during which the bile duct cannula was elevated until bile flow decreased to 1/3 the basal rate, and a 2-hr period after release of hydrostatic biliary pressure. We found that pressure treatment caused biliary concentrations of glutathione to progressively decrease by 80%, while biliary Pi rapidly rose approximately 3- to 4-fold, bile salt gradually increased approximately 3-fold, and biliary glucose concentration progressively rose 15-fold. HPLC analysis of monobromobimane-derivatized biliary thiols indicated that the decline in biliary glutathione was not accompanied by an increase in its breakdown products, cysteine and cysteinylglycine. Pressure treatment led to four patterns of change in biliary amino acid concentrations: (1) increases of 29 to 76% for the basic amino acids lysine and arginine, which have very low bile/plasma ratios of about 0.1; (2) no change for the more water soluble amino acids with bile/plasma ratios close to 1.0, e.g., histidine and urea; (3) modest decreases of 16 to 48% for a variety of amino acids including serine, glutamate, and glycine; and (4) marked, progressive decreases of > 50% for aromatic and branched chain amino acids. By 2 hr after release of pressure, only the alterations in biliary glucose and some amino acids, particularly the branched chains, persisted. This is the first report of cholestasis-induced alterations in biliary amino acids.
我们研究了胆汁压力短暂升高对大鼠胆汁中谷胱甘肽和氨基酸的影响。监测的其他胆汁溶质包括总胆汁盐、作为细胞旁渗漏假定标志物的无机磷酸盐（Pi）以及从胆道重吸收的葡萄糖。实验在麻醉大鼠上进行，十二指肠内注入牛磺胆酸盐以在2小时基础期维持胆汁流动，在4小时压力期将胆管插管抬高直至胆汁流量降至基础速率的1/3，之后是2小时静水胆汁压力释放期。我们发现压力处理导致胆汁中谷胱甘肽浓度逐渐降低80%，而胆汁Pi迅速升高约3至4倍，胆汁盐逐渐增加约3倍，胆汁葡萄糖浓度逐渐升高15倍。对单溴代双马来酰亚胺衍生的胆汁硫醇进行高效液相色谱分析表明，胆汁谷胱甘肽的下降并未伴随其分解产物半胱氨酸和半胱氨酰甘氨酸的增加。压力处理导致胆汁氨基酸浓度出现四种变化模式：（1）碱性氨基酸赖氨酸和精氨酸增加29%至76%，其胆汁/血浆比值非常低，约为0.1；（2）胆汁/血浆比值接近1.0的水溶性较高的氨基酸，如组氨酸和尿素，无变化；（3）包括丝氨酸、谷氨酸和甘氨酸在内的多种氨基酸适度降低16%至48%；（4）芳香族和支链氨基酸显著且逐渐降低>50%。压力释放后2小时，只有胆汁葡萄糖和一些氨基酸的变化持续存在，特别是支链氨基酸。这是关于胆汁淤积引起胆汁氨基酸变化的首次报道。
