Protective effect of a human C5a receptor antagonist against hepatic ischaemia-reperfusion injury in rats
Protective effect of a human C5a receptor antagonist against hepatic ischaemia-reperfusion injury in rats
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DOI：
10.1016/j.jhep.2004.02.017
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发表时间：
2004-06-01
影响因子：
25.7
通讯作者：
Taylor, SM
中科院分区：
文献类型：
--
作者：
Arumugam, TV;Woodruff, TM;Taylor, SM
背景/目的：补体激活是由缺血再灌注(I/R)引起的，补体因子C5a在器官特异性I/R损伤中起重要作用。观察小分子C5a受体拮抗剂对大鼠肝脏I/R损伤的保护作用。方法：复制大鼠全肝缺血或部分肝缺血模型，再灌流一段时间。C5aR拮抗剂ACF-[OPdChaWR]静脉注射1 mg/kg。或10 mg/kg灌胃。或者南加州大学。在引发脑缺血之前。结果：C5aR拮抗剂治疗可降低大鼠肝脏I/R后总死亡率、肝组织或血清肿瘤坏死因子α水平、肝肺髓过氧化物酶活性、中性粒细胞数和肝组织病理学改变。在部分肝I/R大鼠，给予C5aR拮抗剂治疗后，肝酶、血清和组织中肿瘤坏死因子α、髓过氧化物酶活性、中性粒细胞浸润和中性粒细胞增多明显减轻，肝组织病理改变也明显减轻。结论：口服活性小分子C5aR拮抗剂能有效降低大鼠肝脏I/R损伤的组织损伤标志物，提示C5a在肝脏I/R损伤中起重要作用。(C)2004年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Complement activation is induced by ischaemia-reperfusion (I/R) and the complement factor C5a plays an important role in organ specific I/R injuries. This study investigated the efficacy of a small molecule C5a receptor (C5aR) antagonist against hepatic I/R injury.Methods: Total hepatic ischaemia or partial hepatic ischaemia were induced in rats, followed by a period of reperfusion. The C5aR antagonist, AcF-[OPdChaWR], was administered at 1 mg/kg i.v. or 10 mg/kg p.o. or s.c. before induction of ischaemia. Total hepatic I/R-induced mortality was measured and partial hepatic ischaemia injury was assessed by measuring the serum levels of liver enzymes, tissue or serum TNFalpha, liver and lung myeloperoxidase activity, the number of infiltrating neutrophils, neutrophilia and liver histopathology.Results: C5aR antagonist treatment reduced total hepatic I/R-induced mortality. In partial hepatic I/R rats, treatment with the C5aR antagonist significantly attenuated the increases in liver enzymes, serum and tissue TNFalpha, myeloperoxidase activity, infiltrating neutrophils, neutrophilia, and also reduced liver histopathology.Conclusions: This study shows that an orally active, small molecule C5aR antagonist is effective in reducing the markers of tissue damage caused by I/R in the rat, suggesting an important role for C5a in I/R injuries in the liver. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.