DETERMINANTS OF GLUTATHIONE EFFLUX AND BILIARY GSH GSSG RATIO IN PERFUSED RAT-LIVER
DETERMINANTS OF GLUTATHIONE EFFLUX AND BILIARY GSH GSSG RATIO IN PERFUSED RAT-LIVER
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DOI：
10.1152/ajpgi.1989.256.3.g482
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发表时间：
1989-03-01
影响因子：
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通讯作者：
BOYER, JL
中科院分区：
文献类型：
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作者：
BALLATORI, N;TRUONG, AT;BOYER, JL
利用分离的灌注大鼠肝脏，我们研究了影响谷胱甘肽[还原性谷胱甘肽（GSH）和谷胱甘肽二硫醚（GSSG）]外排到灌注液和胆汁中的几个因素，包括灌注液成分、向肝脏的氧输送和活性肽（AT-125） （γ的抑制剂）的影响。-谷氨酰转移酶活性。当肝脏灌注再循环的克雷布斯-林格碳酸氢盐缓冲液时，只有7-26%释放的谷胱甘肽以氧化形式排泄到胆汁中（71-90%为GSSG）。相比之下，当以20%的牛红细胞或20%的氟碳乳液作为灌注液时，胆道谷胱甘肽占肝外排总量的比例较大（16-41%），仅39-65%作为GSSG排出。为了确定氧气输送到肝脏是否可以解释其中的一些差异，我们测量了胆和谷胱甘肽的流出量，因为O2输送的变化包括：1)增加灌注流速，2)改变氟碳乳液的浓度（5、10和20%），以及3)改变PO2 （95% O2-5% CO2 vs. 50% O2-5% CO2-45% N2）。在所有实验条件下，氧气输送的增加都伴随着胆汁流量的增加和谷胱甘肽流出到胆汁中的浓度和速率的增加，但谷胱甘肽的正弦流出没有显著变化。肝组织GSH和GSSG水平不受各种治疗的影响。当可以利用。-谷氨酰转移酶活性被AT-125抑制，胆汁谷胱甘肽升高至。在氟碳灌注的肝脏中，50%的肝外排，只有24-29%的谷胱甘肽以GSSG的形式排出。与胆汁谷胱甘肽外排相反，灌注液的组成和AT-125都没有影响谷胱甘肽外排到灌注液中。这些结果表明，胆汁是灌注大鼠肝脏中肝谷胱甘肽外排的主要途径。胆道谷胱甘肽外排速率及其氧化还原状态均受灌注液组成、流速、氧向肝脏的输送以及γ酶活性的影响。谷酰基转移酶。
Utilizing the isolated perfused rat liver, we examined several factors influencing efflux of glutathione [reduced glutathione (GSH) and glutathione disulfide (GSSG)] into perfusate and bile, including the effects of perfusate composition, oxygen delivery to the liver, and acivicin (AT-125), an inhbitor of .gamma.-glutamyl transferase activity. When livers were perfused with a recirculating Krebs-Ringer bicarbonate buffer only 7-26% of released glutathione was excreted into bile, mainly in its oxidized form (71-90% as GSSG). In contrast, when 20% bovine red blood cells or 20% fluorocarbon emulsion were utilized as perfusates, biliary glutathione accounted for a larger fraction of total hepatic efflux (16-41%), and only 39-65% was excreted as GSSG. To determine whether O2 delivery to the liver could explain some of these differences, biliary and sinusoidal efflux of glutathione were measured as O2 delivery was varied by 1) increasing the perfusion flow rate, 2) altering the concentration of fluorocarbon emulsion (5, 10, and 20%), and 3) changing the PO2 (95% O2-5% CO2 vs. 50% O2-5% CO2-45% N2). Under all experimental conditions, an increase in O2 delivery was accompanied by an increase in bile flow and in the concentration and rate of glutathione efflux into bile but not significant change in sinusoidal efflux of glutathione. Hepatic tissue GSH and GSSG levels were not affected by various treatments. When .gamma.-glutamyl transferase activity was inhibited with AT-125, biliary glutathione increased to levels of .apprx.50% of total hepatic efflux in fluorocarbon-perfused livers, and only 24-29% of the glutathione was excreted as GSSG. In contrast to biliary glutathione efflux, neither the composition of perfusate nor AT-125 had any effect of efflux of glutathione into perfusate. These findings indicate that bile is the major route of hepatic glutathione efflux in perfused rat liver. Both the rate of biliary glutathione efflux and its redox status are influenced by perfusate composition, flow rate, O2 delivery to the liver, and the activity of the enzyme .gamma.-glutamyl transferase.