Unité Chronothérapie, Cancers et Transplantation, Université Paris-Saclay, 94800 Villejuif, France.
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Catalonia, Spain.
Int J Mol Sci. 2022 Oct 20;23(20):12615. doi: 10.3390/ijms232012615.
The scarcity of livers for transplantation is rising, and new strategies to extend the donor pool are being explored. One solution is to use marginal grafts from extended criteria donors, presenting, for example, liver steatosis. As current preservation solutions (UW, HTK, and IGL-1) were mainly designed for static cold storage (SCS) only, IGL-2, a modified version of IGL-1, was developed to be suitable for SCS and dynamic preservation, such as hypothermic oxygenated perfusion (HOPE). In this study, we investigated the combined effect of IGL-2, SCS, and HOPE and compared it to the most used preservation solution (UW and Belzer MPS). Four experimental groups with six rats each were designed using Zucker rats. All groups underwent 24 h of SCS (in IGL-2 or UW) + 2 h of normothermic machine perfusion (NMP) at 37 °C to mimic transplantation. HOPE (IGL-2 or Belzer MPS) was performed before NMP on half of the rats. The IGL-2 group demonstrated lower transaminases and a significantly low level of glycocalyx proteins, CASP3, and HMGB1 in the perfusates. These data suggest the protective role of IGL-2 for fatty livers in preserving the endothelial glycocalyx, apoptosis, and inflammation.
肝脏供体的短缺日益严重,人们正在探索新的策略来扩大供体库。一种解决方案是使用边缘供体的移植肝脏,这些供体可能存在肝脂肪变性等问题。由于目前的保存溶液(UW、HTK 和 IGL-1)主要是为静态冷藏(SCS)设计的,因此开发了 IGL-2,这是 IGL-1 的改良版本,适用于 SCS 和动态保存,如低温氧合灌注(HOPE)。在这项研究中,我们研究了 IGL-2、SCS 和 HOPE 的联合作用,并将其与最常用的保存溶液(UW 和 Belzer MPS)进行了比较。使用 Zucker 大鼠设计了四个每组六只大鼠的实验组。所有组均接受 24 h 的 SCS(在 IGL-2 或 UW 中)+ 2 h 的常温机器灌注(NMP),以模拟移植。HOPE(IGL-2 或 Belzer MPS)在 NMP 前在一半大鼠中进行。IGL-2 组在灌流液中显示出较低的转氨酶和糖萼蛋白、CASP3 和 HMGB1 的水平显著降低。这些数据表明,IGL-2 在保存内皮糖萼、细胞凋亡和炎症方面对脂肪肝具有保护作用。