Koeppel T A, Trauner M, Mennone A, Arrese M, Rios-Velez L, Boyer J L
Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT 06520-8019, USA.
J Hepatol. 1998 May;28(5):812-9. doi: 10.1016/s0168-8278(98)80231-6.
BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown.
We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired.
Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage.
We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.
背景/目的：肝移植患者冷缺血后的肝脏再灌注常伴有胆汁流量减少。谷胱甘肽是胆汁酸非依赖性胆汁流量的主要决定因素，而冷缺血对胆汁中谷胱甘肽排泄的影响尚不清楚。
我们在循环系统中研究了冷缺血（威斯康星大学溶液（4℃），24小时）及随后的再灌注（100分钟）对胆汁中谷胱甘肽排泄的影响。由于谷胱甘肽可能是胆道内一种重要的抗氧化剂，再灌注期间胆道内的氧化应激可能有助于肝移植后胆管损伤的发病机制，我们还评估了谷胱甘肽胆汁排泄已受损的突变型TR-/-大鼠再灌注肝脏的胆管形态。
冷缺血后再灌注的Wistar大鼠肝脏中肝胆汁形成减少。胆汁中谷胱甘肽浓度和排出量显著降低，并与缺血后胆汁分泌变化相关。仅在再灌注开始后立即检测到胆汁中氧化型谷胱甘肽/谷胱甘肽比值增加，表明存在氧化应激。在对照灌注肝脏中已经显著降低的TR-/-大鼠肝脏基础胆汁流速，在再灌注早期而非后期进一步降低。Wistar和TR-/-大鼠肝脏的再灌注均未出现胆管损伤的电子显微镜证据。
我们得出结论，谷胱甘肽的胆汁排泄受损导致冷缺血后胆汁流量减少。在离体灌注大鼠肝脏中，缺乏胆汁谷胱甘肽似乎不会促进再灌注期间胆管损伤的超微结构证据。
