Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers
Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers
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DOI：
10.1097/00007890-200204150-00005
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发表时间：
2002-04-15
期刊：
影响因子：
6.2
通讯作者：
Todo, S
中科院分区：
文献类型：
--
作者：
Ishikawa, H;Jin, MB;Todo, S
背景。在一系列的犬肝缺血实验中，我们发现可以通过抑制血管收缩、细胞因子产生、血小板聚集和中性粒细胞浸润来改善肝损伤。环二磷酸腺苷（cAMP）被认为与大多数此类事件有关。在我们的研究中，我们测试了我们的假设，即通过磷酸二酯酶 (PDE) 3 抑制剂氨力农 (AM) 或腺苷酸环化酶刺激剂 NKH477 (NKH) 增强内源性 cAMP，可以减轻肝脏的缺血和再灌注损伤。使用了三十六只小猎犬。他们被分为CT组（未治疗对照）、AM组、NKH组和CB组（两种药物治疗）。 AM 或 NKH 静脉注射缺血前 1 小时（preAM 组和 preNKH 组）或再灌注前 15 分钟（pos-AM 和 postNKH）。组合组动物仅在缺血前接受治疗。分析动物存活率、肝组织血流量、肝酶、血小板计数、能量代谢、肝cAMP和环鸟苷3',5'-环单磷酸水平以及组织病理学。结果。通过使用任一药物进行治疗前或治疗后，两周的动物存活率显着提高。再灌注后，肝组织血流量、肝酶释放、血小板计数、能量代谢、组织cAMP水平和组织学结构也显着改善。两者张力的结合。 AM 治疗比 NKH 表现出更多的保护作用，特别是在缺血前进行治疗时。有趣的是，不仅环鸟苷3',5'-环单磷酸在通过缺血前治疗再灌注后也恢复到较高水平。结论。施用氨力农或NKH477可维持肝组织中环核苷酸的浓度，并减轻肝脏的缺血和再灌注损伤。因此，调节肝组织环核苷酸是肝脏保存和手术中预防肝损伤的重要选择。
Background. In a series of canine liver ischemia experiments, we have shown that amelioration of hepatic injury is achievable by the inhibition of vasoconstriction, cytokine production, platelet aggregation, and neutrophil infiltration. Cyclic adenosine diphosphate (cAMP) was considered to be involved in most of these events. In our study, we tested our hypothesis that augmentation of endogenous cAMP by phosphodiesterase (PDE) 3 inhibitor, amrinone (AM), or adenylate cyclase stimulator, NKH477 (NKH), could attenuate ischemia and reperfusion injury of the liver.Methods. Thirty-six beagle dogs were used. They were divided into group CT (untreated control), group AM, group NKH, and group CB (treated by both agents). AM or NKH were administered i.v. 1 hr before ischemia (group preAM and group preNKH) or 15 min before reperfusion (pos-AM and postNKH). Combination group animals were treated only before ischemia. Animal survival, hepatic tissue blood flow, liver enzymes, platelet counts, energy metabolism, hepatic cAMP and cyclic guanosine 3',5'-cyclic monophosphate levels, and histopathology were analyzed.Results. Two-week animal survival was significantly improved by pre- or posttreatment with either agent. After reperfusion, hepatic tissue blood flow, liver enzyme release, platelet counts, energy metabolism, tissue cAMP levels, and histological architecture were also ameliorated markedly. Combination of both tension. AM treatment exhibited more protective effects than NKH, particularly when it was given before ischemia. Interestingly, not only cyclic guanosine 3',5'-cyclic monophosphate, were also restored at higher levels after reperfusion by preischemia treatment.Conclusions. Administration of amrinone or NKH477 maintained hepatic tissue concentrations of cyclic nucleotides, and attenuated ischemia and reperfusion injury of the liver. Thus, regulation of hepatic tissue cyclic nucleotides is an important alternative for prevention of hepatic damage in liver preservation and surgery.