Department of Clinical Sciences, Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina; and.
Department of Population Health and Pathobiology, Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina.
Am J Physiol Gastrointest Liver Physiol. 2015 Jan 15;308(2):G63-75. doi: 10.1152/ajpgi.00112.2013. Epub 2014 Nov 20.
Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury.
在缺血再灌注损伤领域的研究中,一直存在着一个问题,即无法将研究结果转化为临床有用的治疗方法。这可能部分与导致肠道缺血的疾病过程的复杂性有关,但也可能是由于选择了不合适的研究模型。研究动物模型是研究缺血再灌注诱导的肠道损伤的重要组成部分。然而,在临床患者中,导致肠道血流受损的临床情况范围广泛,从原发性肠道疾病到继发于远处器官衰竭和全身性疾病的情况都有。因此,与诸如肠扭转、休克和坏死性小肠结肠炎等差异很大的临床情况下的人类病理情况非常相似的模型,很可能为理解可能最终转化为患者治疗的缺血机制提供最大的机会。此外,导致不同程度缺血的情况可能会因血液重新灌注到组织中而变得更加复杂,在某些情况下,这会进一步加重损伤。本综述评估了缺血再灌注损伤的动物模型,以及从每种模型中获得的知识,以帮助选择合适的研究模型。此外,还讨论了肠道缺血再灌注研究的未来,以确定从缺血再灌注损伤的持续研究中最有可能受益的领域。
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