Kumar Arvind, Palek Richard, Liska Vaclav
Biomedical Center, Charles University, Faculty of Medicine in Pilsen, Pilsen, Czech Republic.
Department of Surgery, Charles University, Faculty of Medicine in Pilsen, Teaching Hospital Pilsen, Pilsen, Czech Republic.
J Clin Exp Hepatol. 2019 May-Jun;9(3):345-353. doi: 10.1016/j.jceh.2018.07.002. Epub 2018 Jul 17.
Given the high mortality rate and clinical impact associated with sinusoidal obstruction syndrome (SOS), many studies have attempted to better characterize the disease and potential treatment strategies. However, the unpredictability of SOS onset represents a major obstacle when developing reproducible and controlled clinical trials in humans. Similarly, although studies have elucidated many of the molecular and cellular mechanisms of SOS, they often lack clinical relevance and translatability, highlighting the importance of experimental research. Animal models have greatly varied in the approach used to induce SOS in accordance with the numerous causes of human disease. Thus far, the most common and prevalent model is the monocrotaline-induced model in rats, which has served as the basis for both new diagnostic and treatment studies and has been revised over the last 20 years to optimize its use. Furthermore, radiotherapy, oxaliplatin-based chemotherapy, and even hematopoietic stem cell transplantation have been recently used to better replicate human SOS in animals. Nevertheless, because of the novelty of such research, further studies should be conducted to better understand the reproducibility and applicability of these newer models. Thus, this review seeks to summarize the methods and results of experimental models of SOS and compare the efficacy of these various adaptations.
鉴于肝窦阻塞综合征(SOS)相关的高死亡率和临床影响,许多研究试图更好地描述该疾病及其潜在的治疗策略。然而,SOS发病的不可预测性在开展可重复且可控的人体临床试验时构成了主要障碍。同样,尽管已有研究阐明了SOS的许多分子和细胞机制,但这些机制往往缺乏临床相关性和可转化性,这凸显了实验研究的重要性。根据人类疾病的多种病因,动物模型在诱导SOS的方法上有很大差异。迄今为止,最常见且普遍使用的模型是大鼠的野百合碱诱导模型,该模型已成为新诊断和治疗研究的基础,并在过去20年中不断修订以优化其应用。此外,放射治疗、基于奥沙利铂的化疗,甚至造血干细胞移植最近也被用于在动物中更好地复制人类SOS。然而,由于此类研究尚属新颖,应进一步开展研究以更好地了解这些新模型的可重复性和适用性。因此,本综述旨在总结SOS实验模型的方法和结果,并比较这些不同改良模型的疗效。