Krähenbühl S, Stucki J, Reichen J
Department of Clinical Pharmacology, University of Berne, Switzerland.
Biochem Pharmacol. 1989 May 15;38(10):1583-8. doi: 10.1016/0006-2952(89)90305-5.
Mitochondrial function is impaired in patients and experimental animals with liver cirrhosis. The relationship between mitochondrial impairment and severity of cirrhosis is unknown, however. We therefore characterized the severity of cirrhosis in rats with phenobarbital/CCl4-induced cirrhosis by the aminopyrine breath test, a microsomal function test reflecting hepatocellular mass. Mitochondrial function was evaluated by measuring oxygen consumption, enzyme activities and ATP production in mitochondria isolated from cirrhotic (N = 8) and control livers (N = 4). Oxygen consumption and mitochondrial enzyme activities calculated per liver were significantly reduced in the presence of cirrhosis. This decrease corresponded to the loss of hepatocytes calculated from the reduction in aminopyrine breath test. The effect of atractylate, oligomycin and dinitrophenol on state 3 respiration was equal between the two groups. The respiratory control ratio was significantly reduced in mitochondria from cirrhotic livers with beta-hydroxybutyrate (4.01 +/- 0.94 vs 5.45 +/- 0.40), but not with succinate as substrate. The rate of ATP production was significantly decreased in mitochondria from cirrhotic rats for both substrates. In contrast, the static head (state 4) phosphate potential was fully developed after 10 min and was equal between the two groups. We conclude that cirrhosis of the liver leads to a loss of hepatocytes which is paralleled by reduced oxygen uptake and reduced mitochondrial enzyme activities.
肝硬化患者和实验动物的线粒体功能受损。然而，线粒体损伤与肝硬化严重程度之间的关系尚不清楚。因此，我们通过氨基比林呼吸试验（一种反映肝细胞量的微粒体功能试验）来表征苯巴比妥/四氯化碳诱导的肝硬化大鼠的肝硬化严重程度。通过测量从肝硬化肝脏（N = 8）和对照肝脏（N = 4）分离的线粒体中的氧气消耗、酶活性和ATP生成来评估线粒体功能。在存在肝硬化的情况下，每肝脏计算的氧气消耗和线粒体酶活性显著降低。这种降低与根据氨基比林呼吸试验的降低计算出的肝细胞损失相对应。两组之间，苍术苷、寡霉素和二硝基苯酚对状态3呼吸的影响相同。以β-羟基丁酸为底物时，肝硬化肝脏线粒体的呼吸控制率显著降低（4.01 +/- 0.94对5.45 +/- 0.40），但以琥珀酸为底物时则不然。两种底物在肝硬化大鼠线粒体中的ATP生成速率均显著降低。相比之下，静态水头（状态4）磷酸势在10分钟后充分发展，两组之间相同。我们得出结论，肝硬化导致肝细胞损失，同时伴有氧气摄取减少和线粒体酶活性降低。
