Remote Ischemic Preconditioning Alleviates Liver Ischemia-reperfusion Injury In A Small-for-size Liver Transplantation Model

BackgroundLiver transplantation (OLTx) is an effective treatment for end-stage liver diseases. However, ischemia/reperfusion (I/R) injury of the liver remains a major cause of graft injury, causing liver dysfunction and even failure posttransplantation. Liver transplantation involves a period of cold and warm ischemia followed by reperfusion which initiates an inflammatory cascade resulting in organ non-function and dysfunction. This is referred to as ischemia reperfusion injury (IRI).Remote ischemic preconditioning (RIPC) is a novel method which entails brief periods of ischemia followed by reperfusion of one organ and results in protection of remote organs from ischemia without direct stress or trauma to blood vessels. It is presumed that remote preconditioning acts by release of biochemical messengers into the circulation or by activation of nerve pathways which confer protection on the remote organ. Studies have been carried out to show the benefit to the heart, lung and kidney after brief ischemia in the mesentery, limb and kidney. None of these studies investigated the effect of RIPC on small graft in 30% liver transplantation model. We focused our study on small graft changes in hepatic IR by RIPC. We hypothesized that RIPC may protect small graft ,probably through HO-1 upregulatory according to previous studies.Objective To investigate the effects of Remote Ischemic Precondition (RIPC) on small-for-size graft ischemia/reperfusion injury in a small-for-size liver transplantation model.Methods A rat model of 30% liver transplantation (30%OLT) was used. Two groups of animals (A: 30% OLT; B: RIPC+30%OLT) were studied (n=5,each group). Expression of hepatic Hemeoxygenase-1(HO-1) protein and mRNA ,serum alanine aminotransferase (ALT) levels, were measured after 2,6,12,24h of transplantation.Results Serum ALT levels(2,6,12,24 h ) in Group A,B were [ (1468.4±71.74)U/L,(480.76±13.34)U/L,(1511.78±20.46)U/L,(101.18±15.99)U/L,(1652.2±38.45)U/L,(1311.98±28.59)U/L,(1130.28±40.96)U/L,(823.88±33.21)U/L].In Group B: Real-time PCR detected mRNA of HO-1 2h after transplantation and persisted 24h. HO-1 protein was induced 6h after transplantation, and persisted for 24h; immunohistochemical staining was responded to western blots.Conclusion RIPC alleviates small-for-size graft ischemia/reperfusion injury . Overexpression of HO-1 play a key role in protection.