Effects of inhibitors of the activity of poly (ADP‐ribose) synthetase on the liver injury caused by ischaemia‐reperfusion: a comparison with radical scavengers
Effects of inhibitors of the activity of poly (ADP‐ribose) synthetase on the liver injury caused by ischaemia‐reperfusion: a comparison with radical scavengers
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聚（ADP-核糖）合成酶活性抑制剂对缺血再灌注肝损伤的影响：与自由基清除剂的比较
DOI：
10.1038/sj.bjp.0701930
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发表时间：
1998
影响因子：
7.3
通讯作者：
C. Thiemermann
中科院分区：
文献类型：
--
作者：
J. Bowes;C. Thiemermann
1聚腺苷二磷酸核糖合成酶（Poly（ADP‐ribose）synthetase，PARS）是一种由活性氧（ROS）和过氧亚硝酸根引起的DNA链断裂激活的核酶。PARS的过度激活可能参与了ROS对体外肝细胞的损伤，PARS活性抑制剂可减轻体内心脏、骨骼肌和脑的再灌注损伤程度。在这里，我们比较了PARS活性的各种抑制剂与去铁胺（铁螯合剂，防止羟基自由基的产生）和铁（超氧阴离子的细胞内清除剂）对麻醉大鼠或兔的肝脏缺血和再灌注引起的肝损伤程度的影响。2大鼠肝脏缺血（30或60 min）和再灌注（120 min）后，血清谷草转氨酶（AST）和丙氨酸转氨酶（ALT）明显升高，提示肝损伤的发生。在再灌注前静脉注射PARS抑制剂3-氨基苯甲酰胺（3-AB，10 mg kg−1或30 mg kg−1）、1，5-二羟基异喹啉（ISO，1 mg kg−1）或4-氨基-1，8-萘二甲酰亚胺（4-AN，3 mg kg−1）并没有降低缺血-再灌注引起的肝损伤程度。3与PARS抑制剂相反，去铁胺（40 mg kg−1）或铁铁（300 mg kg−1）显著减弱了大鼠肝脏缺血-再灌注引起的血清AST和ALT水平的升高。4在家兔中，缺血（60分钟）和再灌注（120分钟）引起的肝损伤程度也不受3-AB（10 mg kg−1）或ISO（1 mg kg−1）的影响。5这些结果支持以下观点：氧源性自由基的产生通过独立于PARS激活的机制介导与缺血性肝脏再灌注相关的肝损伤。
1 Poly (ADP‐ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA which are caused by reactive oxygen species (ROS) and peroxynitrite. Excessive activation of PARS may contribute to the hepatocyte injury caused by ROS in vitro and inhibitors of PARS activity reduce the degree of reperfusion injury of the heart, skeletal muscle and brain in vivo. Here we compared the effects of various inhibitors of the activity of PARS with those of deferoxamine (an iron chelator which prevents the generation of hydroxyl radicals) and tiron (an intracellular scavenger of superoxide anion) on the degree of hepatic injury caused by ischaemia and reperfusion of the liver in the anaesthetized rat or rabbit. 2 In the rat, ischaemia (30 or 60 min) and reperfusion (120 min) of the liver resulted in significant increases in the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) indicating the development of liver injury. Intravenous administration of the PARS inhibitors 3‐aminobenzamide (3‐AB, 10 mg kg−1 or 30 mg kg−1), 1,5‐dihydroxyisoquinoline (ISO, 1 mg kg−1) or 4‐amino‐1,8‐naphthalimide (4‐AN, 3 mg kg−1) before reperfusion did not reduce the degree of liver injury caused by ischaemia‐reperfusion. 3 In contrast to the PARS inhibitors, deferoxamine (40 mg kg−1) or tiron (300 mg kg−1) significantly attenuated the rise in the serum levels of AST and ALT caused by ischaemia‐reperfusion of the liver of the rat. 4 In the rabbit, the degree of liver injury caused by ischaemia (60 min) and reperfusion (120 min) was also not affected by 3‐AB (10 mg kg−1) or ISO (1 mg kg−1). 5 These results support the view that the generation of oxygen‐derived free radicals mediates the liver injury associated with reperfusion of the ischaemic liver by mechanism(s) which are independent of the activation of PARS.
抑制聚（ADP-核糖）聚合酶对肝细胞和成纤维细胞氧化细胞损伤过程的不同影响。
影响因子：
5.8
作者：
Yamamoto,K;Tsukidate,K;Farber,JL
通讯作者：
Farber,JL
影响因子：
3.4
作者：
BERGER, NA
通讯作者：
BERGER, NA
影响因子：
3.7
作者：
CARSON, DA;SETO, S;CARRERA, CJ
通讯作者：
CARRERA, CJ