Influence of 5-aminoisoquinolin-1-one (5-AIQ) on neutrophil chemiluminescence in rats with transient and prolonged focal cerebral ischemia and after reperfusion.
Influence of 5-aminoisoquinolin-1-one (5-AIQ) on neutrophil chemiluminescence in rats with transient and prolonged focal cerebral ischemia and after reperfusion.
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发表时间：
2008-12
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通讯作者：
S. Hendryk;Z. Czuba;H. Jędrzejowska‐Szypułka;E. Szliszka;V. Phillips;M. Threadgill;W. Krol
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作者：
S. Hendryk;Z. Czuba;H. Jędrzejowska‐Szypułka;E. Szliszka;V. Phillips;M. Threadgill;W. Krol
不同因素刺激中性粒细胞会增加其氧化活性，产生的自由基可反映活化程度。聚腺苷5 '-二磷酸核糖聚合酶-1（Poly（adenosine 5'-diphosphate ribose）polymerase-1，PARP-1）是一种由DNA链断裂激活的核酶，在缺血再灌注损伤和炎症相关的组织损伤中起重要作用。5-氨基异喹啉-1-酮（5-AIQ）是大鼠体内和体外PARP-1活性的强效抑制剂。急性（80分钟）和长期（24小时）局灶性脑缺血大鼠大脑中动脉阻塞，有或没有再灌注，有或没有管理的5-AIQ。中性粒细胞的氧化活性用化学发光法测定。给予5-AIQ.HCl（3.0 mg kg（-1）b.w. - （i.v.）与对照组相比，在经历慢性缺血24小时的组中引起嗜中性粒细胞氧化活性的显著降低，但在接受80分钟缺血的组中没有显著作用。中性粒细胞的氧化活性的增加被证实在大鼠长期脑缺血，然后再灌注。5-AIQ可能通过抑制局部缺血灶中的PARP-1以及因此降低活化的中性粒细胞的炎症介质表达来降低这种活性。
Stimulation of neutrophils by different factors increases their oxidative activity and the free radicals produced can report on the degree of activation. Poly(adenosine 5'-diphosphate ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation. 5-aminoisoquinolin-1-one (5-AIQ) is a potent inhibitor of PARP-1 activity in vitro and in vivo in rats. Acute (80 min) and prolonged (24h) focal cerebral ischaemia was induced in rats by obstruction of the median cerebral artery, with or without reperfusion, with or without administration of 5-AIQ. The oxidative activity of neutrophils was measured by chemiluminescence. Administration of 5-AIQ.HCl (3.0 mg kg(-1) b.w. - i.v.) caused a significant decrease in the oxidative activity of neutrophils in the group which had experienced chronic ischaemia for 24h but had no significant effect in the group which had received 80 min ischaemia, when compared to the control group. Increase of the oxidative activity of neutrophils was confirmed in rats with prolonged cerebral ischaemia, followed by reperfusion. 5-AIQ probably may decrease this activity through inhibition of PARP-1 in focus of local ischaemia as well as hence lowering the expression of inflammatory mediators by activated neutrophils.