Denno R, Takabayashi A, Sugano M, Awane M, Jin M B, Morimoto T, Tanaka K, Yamaoka Y, Kobayashi N, Ozawa K
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
J Gastroenterol. 1995 Jun;30(3):338-46. doi: 10.1007/BF02347509.
Controversy persists as to whether reperfusion-induced injuries actually occur in the hepatocyte. The liver is the major source of glutathione, a scavenger of hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as an index of hepatic metabolic stress. A total of 121 rats were studied. The superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by 0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver, bile, and plasma were quantified, using glutathione reductase-coupled enzymatic assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level and energy charge potential. However, plasma levels of total glutathione and GSSG in the inferior vena cava increased after SMV occlusion and continued to increase after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the SMV, and remained low even after reperfusion. The liver maintains homeostasis despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into the hepatic vein when the SMV is occluded. We conclude that the total amount of glutathione and GSSG in the plasma is directly correlated with oxidative stress in the liver.
关于再灌注诱导的损伤是否真的发生在肝细胞中，争议仍然存在。肝脏是谷胱甘肽的主要来源，谷胱甘肽是一种过氧化氢清除剂。本研究的目的是评估还原型谷胱甘肽（GSH）与氧化型谷胱甘肽（GSSG）的比值[GSH:GSSG]作为肝脏代谢应激指标的敏感性。共研究了121只大鼠。肠系膜上静脉（SMV）闭塞30分钟，然后再灌注0、10或120分钟。使用谷胱甘肽还原酶偶联酶法对肝脏、胆汁和血浆中的总谷胱甘肽和GSSG水平进行定量。结果表明，尽管三磷酸腺苷（ATP）水平和能量电荷电位降低，但SMV闭塞后肝脏的GSH/GSSG比值仍保持不变。然而，SMV闭塞后下腔静脉血浆中总谷胱甘肽和GSSG水平升高，再灌注后继续升高。SMV闭塞30分钟期间胆汁GSSG流出减少，再灌注后仍保持在低水平。尽管胆汁GSSG流出减少，但肝脏可能通过在SMV闭塞时将过量的GSSG分泌到肝静脉中来维持内环境稳定。我们得出结论，血浆中谷胱甘肽和GSSG的总量与肝脏中的氧化应激直接相关。
