The effect of antagonism of adenosine A1 receptor against ischemia and reperfusion injury of the liver
The effect of antagonism of adenosine A1 receptor against ischemia and reperfusion injury of the liver
复制标题
DOI：
10.1016/j.jss.2006.09.021
复制
发表时间：
2007-05-01
影响因子：
2.2
通讯作者：
Todo, Satoru
中科院分区：
文献类型：
--
作者：
Magata, Shinichiro;Taniguchi, Masahiko;Todo, Satoru
背景。已知腺苷在肝脏缺血再灌注损伤中发挥保护作用，但并非所有腺苷受体都发挥细胞保护作用。我们已经验证了我们的假设，即通过其拮抗剂KW3902[8-（去甲金刚烷-3-基）-1,3-二丙基黄嘌呤]阻断腺苷与A受体的结合可减轻肝缺血-再灌注损伤。成年雌性比格犬接受2小时全肝血管排除术（THVE）和静脉-静脉旁路术。对照组为行静脉-静脉旁路治疗的未治疗动物（CT组，n = 6）。KW3902在缺血前以1 μ g/kg/min的剂量连续给药60min （KW组，n = 6）。研究两周存活率、血流动力学、肝组织血流量（HTBF）、肝功能、能量代谢、cAMP浓度及组织病理学结果。与CT组相比，KW组两周动物存活率显著提高（CT组：16.7%，KW组：83.3%）。KW组HTBF、肝功能、肝腺嘌呤核苷酸浓度明显优于CT组。此外，KW组cAMP浓度维持显著高于CT组。组织病理学检查显示，kw组肝脏结构得以保留，中性粒细胞向肝组织浸润受到抑制。缺血前给予腺苷A受体拮抗剂可减轻肝缺血再灌注。受伤。为了发挥腺苷对肝脏缺血再灌注损伤的有益作用，必须抑制腺苷A1受体的激活。(c) 2007爱思唯尔公司版权所有。
Background. Adenosine is known to exert protective roles in hepatic ischemia and reperfusion injury, while all adenosine receptors do not play the cytoprotective roles. We have tested our hypothesis that blockage of adenosine binding to A, receptor by its antagonist, KW3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] attenuates hepatic ischemia-reperfusion injury.Methods. Adult female beagle dogs underwent a 2 h total hepatic vascular exclusion (THVE) with a veno-venous bypass. Nontreated animals that underwent THVE with a venovenous bypass alone were used as the control (Group CT, n = 6). KW3902 was given to the animals by continuous intraportal infusion for 60 min before ischemia at a dose of 1 mu g/kg/min (Group KW, n = 6). Two wk survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, energy metabolism, cAMP concentration, and histopathological findings were studied.Results. Two wk animal survival was significantly improved in group KW compared with that in group CT (group CT: 16.7% versus group KW: 83.3%). HTBF, liver function, and hepatic adenine nucleotide concentration were remarkably better in group KW than group CT. In addition, cAMP concentration in group KW was maintained significantly higher than group CT. Histopathological examination revealed preservation of hepatic architecture and suppression of neutrophil infiltration into hepatic tissue in group KW.Conclusion. Administration of adenosine A, receptor antagonist before ischemia attenuates hepatic ischemia-reperfusion. injury. To elicit the beneficial effect of adenosine against ischemia and reperfusion injury of the liver, it is important to oppose adenosine A1 receptor activation. (c) 2007 Elsevier Inc. All rights reserved.