Centers for Personalized Diagnostics and for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Methods Mol Biol. 2021;2225:275-292. doi: 10.1007/978-1-0716-1012-1_16.
Ischemia-reperfusion injury (IRI) drives early and long-term damage to organs as well as compounding damage from acute transplant rejection and surgical trauma. IRI initiates an aggressive and prolonged inflammation leading to tissue injury, organ failure, and death. However, there are few effective therapeutic interventions for IRI. The destructive inflammatory cell activity in IRI is part of an aberrant innate immune response that triggers multiple pathways. Hence, immune-modulating treatments to control pathways triggered by IRI hold great therapeutic potential. Viruses, especially large DNA viruses, have evolved highly effective immune-modulating proteins for the purpose of immune evasion and to protect the virus from the host immune defenses. A number of these immune-modulating proteins have proven therapeutically effective in preclinical models, many with function targeting pathways known to be involved in IRI. The use of virus-derived immune-modulating proteins thus represents a promising source for new treatments to target ischemia-reperfusion injury. Laboratory small animal models of IRI are well established and are able to reproduce many aspects of ischemia-reperfusion injury seen in humans. This chapter will discuss the methods used to perform the IRI procedure in mice, as well as clinically relevant diagnostic tests to evaluate liver injury and approaches for assessing histological damage while testing novel immune modulating protein treatments.
缺血再灌注损伤（IRI）可导致器官的早期和长期损伤，并且会加重急性移植排斥反应和手术创伤造成的损伤。IRI 会引发强烈而持久的炎症，导致组织损伤、器官衰竭和死亡。然而，目前针对 IRI 的有效治疗干预措施却很少。IRI 中破坏性的炎症细胞活性是异常固有免疫反应的一部分，它会触发多种途径。因此，免疫调节治疗以控制 IRI 引发的途径具有很大的治疗潜力。病毒，尤其是大型 DNA 病毒，已经进化出高度有效的免疫调节蛋白，用于免疫逃避和保护病毒免受宿主免疫防御。许多这些免疫调节蛋白已被证明在临床前模型中具有治疗效果，其中许多功能针对已知与 IRI 相关的途径。因此，使用病毒衍生的免疫调节蛋白代表了一种有前途的新治疗方法，可以针对缺血再灌注损伤。IRI 的实验室小动物模型已经建立得很好，能够再现人类中许多缺血再灌注损伤的方面。本章将讨论在小鼠中进行 IRI 手术的方法，以及评估肝损伤的临床相关诊断测试和评估组织学损伤的方法，同时测试新型免疫调节蛋白治疗方法。
