Institute of Pathology, University of Bern, Switzerland.
Ann Med. 2012 May;44(3):205-17. doi: 10.3109/07853890.2010.535556. Epub 2011 Jan 24.
Reperfusion of an organ following prolonged ischemia instigates the pro-inflammatory and pro-coagulant response of ischemia / reperfusion (IR) injury. IR injury is a wide-spread pathology, observed in many clinically relevant situations, including myocardial infarction, stroke, organ transplantation, sepsis and shock, and cardiovascular surgery on cardiopulmonary bypass. Activation of the classical, alternative, and lectin complement pathways and the generation of the anaphylatoxins C3a and C5a lead to recruitment of polymorphonuclear leukocytes, generation of radical oxygen species, up-regulation of adhesion molecules on the endothelium and platelets, and induction of cytokine release. Generalized or pathway-specific complement inhibition using protein-based drugs or low-molecular-weight inhibitors has been shown to significantly reduce tissue injury and improve outcome in numerous in-vitro, ex-vivo, and in-vivo models. Despite the obvious benefits in experimental research, only few complement inhibitors, including C1-esterase inhibitor, anti-C5 antibody, and soluble complement receptor 1, have made it into clinical trials of IR injury. The results are mixed, and the next objectives should be to combine knowledge and experience obtained in the past from animal models and channel future work to translate this into clinical trials in surgical and interventional reperfusion therapy as well as organ transplantation.
器官在长时间缺血后再灌注会引发缺血/再灌注（IR）损伤的促炎和促凝反应。IR 损伤是一种广泛存在的病理学现象，在许多临床相关情况下都有观察到，包括心肌梗死、中风、器官移植、脓毒症和休克，以及心肺旁路手术中的心血管手术。经典途径、替代途径和凝集素补体途径的激活以及过敏毒素 C3a 和 C5a 的产生导致多形核白细胞的募集、自由基氧物种的产生、内皮细胞和血小板上黏附分子的上调以及细胞因子的释放。使用基于蛋白质的药物或低分子量抑制剂对补体进行全身性或途径特异性抑制已被证明可显著减少组织损伤并改善众多体外、离体和体内模型中的预后。尽管在实验研究中具有明显的益处，但只有少数补体抑制剂，包括 C1-酯酶抑制剂、抗 C5 抗体和可溶性补体受体 1，已进入 IR 损伤的临床试验。结果喜忧参半，下一个目标应该是结合过去从动物模型中获得的知识和经验，并将其未来的工作重点转移到转化为手术和介入再灌注治疗以及器官移植中的临床试验。
