Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, MA 02114, United States.
World J Gastroenterol. 2013 Aug 7;19(29):4638-50. doi: 10.3748/wjg.v19.i29.4638.
The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications post-transplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies. The methods span the spectrum of encouraging donor weight loss, employing drug therapy, heat shock preconditioning, ischemia preconditioning and selective anesthesia on donors, and the treatment on isolated grafts during preservation. These methods work at different stages of transplantation process, although share similar molecular mechanisms including lipid metabolism stimulation through enzymes or nuclear receptor e.g., peroxisomal proliferator-activated receptor, or anti-inflammation through suppressing cytokines e.g., tumor necrosis factor-α, or antioxidant therapies to alleviate oxidative stress. This similarity of molecular mechanisms implies possible future attempts to reinforce each approach by repeating the same treatment approach at several stages of procurement and preservation, as well as utilizing these alternative approaches in tandem.
供体肝脏短缺导致越来越多地使用扩展标准供体的器官。其中包括脂肪变性的肝脏,这是一种代谢异常,增加了移植后移植物并发症的可能性。在简要介绍了肝脂肪变性的病因、病理生理学、分类和实验模型后,我们在此回顾了应用于临床和实验研究的在移植前拯救脂肪变性供体肝脏的方法。这些方法涵盖了鼓励供体减肥、药物治疗、热休克预处理、缺血预处理和对供体选择性麻醉以及在保存期间对分离移植物进行处理等方面。这些方法在移植过程的不同阶段发挥作用,尽管它们具有相似的分子机制,包括通过酶或核受体(例如过氧化物酶体增殖物激活受体)刺激脂质代谢,或通过抑制细胞因子(例如肿瘤坏死因子-α)来抗炎,或抗氧化治疗以减轻氧化应激。这种分子机制的相似性意味着未来可能会尝试通过在获取和保存的几个阶段重复相同的治疗方法,以及同时使用这些替代方法来加强每种方法。