Kamiike W, Nakahara M, Nakao K, Koseki M, Nishida T, Kawashima Y, Watanabe F, Tagawa K
Transplantation. 1985 Jan;39(1):50-5. doi: 10.1097/00007890-198501000-00005.
The influence of the cellular level of adenosine triphosphate (ATP) in the liver on bile excretion was studied in rats. In ischemia, the cellular ATP level decreased rapidly--and, concomitantly, bile flow stopped within 5 min. Administration of L-ethionine i.p. to rats reduced the bile flow rate with decrease in the cellular ATP level. The correlation between the bile flow rate and the cellular ATP level was confirmed in a liver perfusion system. On anoxic perfusion, the ATP level and bile flow rate changed in the same manner as in ischemia. The recovery rates of both on reoxygenation decreased with increase in the anoxic perfusion period. During perfusion under oxygenated conditions, decrease in cellular ATP to various levels by infusion of various concentrations of potassium cyanide, an inhibitor of respiration, resulted in corresponding and concomitant suppression of bile excretion. Kinetic analysis of the bile flow rate revealed a Michaelis-Menten-type curve for the cellular ATP level. The apparent Kms for ATP of bile flow rate in L-ethionine-treated rat liver and liver perfused with potassium cyanide were 1.0 and 1.6 mM, and their Vmax values were 4.1 and 2.5 microliter/min/g liver, respectively. The concentrations of main bile components, such as phospholipids, cholesterol, and taurocholate increased, but their total outputs decreased with decrease in the ATP level, and returned to the normal range with recovery of the ATP level. Thus, it was shown experimentally that the extent of hepatic injury can be assessed simply by monitoring the bile flow rate, which reflects the cellular level of ATP.
在大鼠中研究了肝脏中三磷酸腺苷（ATP）的细胞水平对胆汁排泄的影响。在缺血时，细胞ATP水平迅速下降，与此同时，胆汁流动在5分钟内停止。腹腔注射L-乙硫氨酸会降低胆汁流速，同时细胞ATP水平也会下降。在肝脏灌注系统中证实了胆汁流速与细胞ATP水平之间的相关性。在缺氧灌注时，ATP水平和胆汁流速的变化与缺血时相同。复氧时两者的恢复率随着缺氧灌注时间的增加而降低。在有氧条件下灌注期间，通过输注不同浓度的呼吸抑制剂氰化钾使细胞ATP降至不同水平，导致胆汁排泄相应并同时受到抑制。胆汁流速的动力学分析显示，细胞ATP水平呈米氏（Michaelis-Menten）型曲线。在L-乙硫氨酸处理的大鼠肝脏和用氰化钾灌注的肝脏中，胆汁流速对ATP的表观米氏常数（Km）分别为1.0和1.6 mM，它们的最大反应速度（Vmax）值分别为4.1和2.5微升/分钟/克肝脏。随着ATP水平的降低，主要胆汁成分如磷脂、胆固醇和牛磺胆酸盐的浓度升高，但其总输出量减少，随着ATP水平的恢复又回到正常范围。因此，实验表明，通过监测反映细胞ATP水平的胆汁流速，可以简单地评估肝损伤的程度。
