Impact of combined ischemic preconditioning and remote ischemic perconditioning on ischemia-reperfusion injury after liver transplantation

Ding-Yang Li,Guang-Yi Wang,Wen-Tao Liu,Xiao-Ju Shi

doi:10.1038/s41598-018-36365-5

Abstract

Ischemic preconditioning (IPC) and remote ischemic perconditioning (RIPer) confer protective effects against liver ischemia-reperfusion injury (IRI), but data about RIPer applying in liver transplantation is lacking. The study aimed to evaluate whether the combination of IPC and RIPer provides reinforced protective effects. C57BL/6 mice (160 pairs) were allocated into four groups: control, subjected to liver transplantation only; IPC, donor hilar was clamped for 10 min followed by 15 min of reperfusion; RIPer, three cycles of occlusion (5 min) and opening (5 min) of femoral vascular bundle were performed before reperfusion; IPC + RIPer, donors and recipients were subjected to IPC and RIPer respectively. Liver tissues were obtained for histological evaluation, TUNEL staining, malondialdehyde assays, GSH-Px assays, and NF-κB p65 protein and Bcl-2/Bax mRNA analyses. Blood samples were used to evaluate ALT, AST, TNF-α, NOx levels and flow cytometry. We found that protective efficacy of RIPer is less than IPC in terms of ALT, TNF-α, GSH-Px and NOx at 2 h postoperation, but almost equivalent at 24 h and 72 h postoperation. Except for Suzuki scores, ALT, Bcl-2/Bax mRNA ratio, other indices showed that combined treatment brought enhanced attenuation in IRI, compared with single treatment, through additive effects on antioxidation, anti-apoptosis, modulation of microcirculation disturbance, and inhibition of innate immune response. This study suggested a combined strategy that could enhance protection against IRI in clinical liver transplantation, otherwise, provided a hint that RIPer’s mechanism might be partly or totally different from IPC in humoral pathway.

Highlights

Liver transplantation, as the only effective therapeutic method for end-stage liver disease, has been widely applied, unavoidable hepatic ischemia-reperfusion injury (IRI) is still challenging for clinicians because of the increased risk for hypohepatia, primary graft failure, allograft vasculopathy, acute rejection reactions, and damage to other major organs[1,2]
IRI remains an inevitable obstacle that could trigger a series of problems after liver transplantation
To the best of our knowledge, this is the first study to report that the combination of ischemic preconditioning (IPC) and remote ischemic perconditioning (RIPer) provides further protection against IRI than either alone using a Mouse orthotopic liver transplantation (MOLT) model

Summary

Introduction

As the only effective therapeutic method for end-stage liver disease, has been widely applied, unavoidable hepatic ischemia-reperfusion injury (IRI) is still challenging for clinicians because of the increased risk for hypohepatia, primary graft failure, allograft vasculopathy, acute rejection reactions, and damage to other major organs[1,2]. This problem needs to be addressed more pressingly with extension of the donor pool using marginal grafts followed by severer IRI3,4. We compared the protective efficacies of the conditioning methods against IRI in terms of liver injury, cell apoptosis, oxidative stress, microcirculation, and inflammatory responses

Methods

Results

Conclusion