Suzuki Shohachi, Inaba Keisuke, Konno Hiroyuki
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Curr Opin Organ Transplant. 2008 Apr;13(2):142-7. doi: 10.1097/MOT.0b013e3282f6a164.
Ischemic preconditioning that consists of a short period of hepatic inflow occlusion followed by reperfusion has the potential to increase tolerance to a subsequent prolonged ischemic insult. This review outlines current insight into ischemic preconditioning for hepatic ischemia and reperfusion injury in experimental and clinical settings.
Experimental evidence suggests that interleukin-6 signaling and increased phosphorylation of STAT3 (signal transducer and activator of transcription-3) are involved in the protective effects of ischemic preconditioning. The benefit of ischemic preconditioning is restricted, however, by old liver and prolonged ischemic time (>60 min). To overcome this, ascorbic acid or glucose administration combined with ischemic preconditioning potentially can maintain the integrity of hepatic mitochondrial function through signal transduction pathways. The influence of ischemic preconditioning on hepatic regeneration varies with partial hepatectomy or small-for-size liver graft models, and remains controversial. Clinically, ischemic preconditioning in deceased donors protects against ischemia and reperfusion injury, as demonstrated by lowered liver enzyme levels, reduced incidence of primary nonfunction, and increased hepatic hypoxia-induced factor-1alpha concentrations.
Enhanced understanding of the mechanisms of organ tolerance induced by ischemic preconditioning would strengthen the significance of this potential therapeutic strategy in liver transplantation.
缺血预处理包括短时间的肝血流阻断随后再灌注,有可能增加对随后长时间缺血损伤的耐受性。本综述概述了目前在实验和临床环境中对肝缺血再灌注损伤的缺血预处理的认识。
实验证据表明,白细胞介素-6信号传导和信号转导及转录激活因子3(STAT3)磷酸化增加参与了缺血预处理的保护作用。然而,缺血预处理的益处受到肝脏老化和长时间缺血时间(>60分钟)的限制。为克服这一问题,给予抗坏血酸或葡萄糖联合缺血预处理可能通过信号转导途径维持肝线粒体功能的完整性。缺血预处理对肝再生的影响因部分肝切除术或小体积肝移植模型而异,仍存在争议。临床上,已故供体的缺血预处理可预防缺血再灌注损伤,这表现为肝酶水平降低、原发性无功能发生率降低以及肝缺氧诱导因子-1α浓度升高。
对缺血预处理诱导器官耐受性机制的深入理解将加强这一潜在治疗策略在肝移植中的重要性。