Isoglycyrrhizinate Magnesium Decreases Ischemic-reperfusion Injury After Liver Transplantation

Part1 Isoglycyrrhizinate magnesium enhances hepatoprotective effect of FK506 on ischemia-reperfusion injury through HMGB1inhibition in a rat model of liver transplantationAbstractBackground:Ischemia-reperfusion injury(IRI)after liver transplantation impairs graft function and affects prognosis of recipients.Isoglycyrrhizinate Magnesium(Iso)is a hepatoprotective drug usually used after liver injury.In this study,we intend to explore whether Iso alone have protective effect after IRI in a rat model of liver transplantataion.We also aimed to study whether Iso could enhance the hepatoprotective effect of Fk506(tacrolimus)and underlying mechanism.Methods:Rats after liver transplantation were treated with different concentration of Fk506 with or without,Iso or lower-dose Fk506 plus Iso.ALT,AST and albumin level were measured by ELISA after 48h,72h and 7days.A cell ischemic/reperfusion model was established to further study the mechanism of hepatoprotective effect of Fk506 and Iso.Results:Iso treatment alone had no effect on liver grafts after LT,but lower-dose Fk506+Iso was better for maintenance of liver function than lower-dose Fk506 alone at 48h,72h and 7days after liver transplantation.In terms of mechanism,Fk506 induced autophagy which resulted in significantly reduced apoptosis and maintained proliferative potential.But autophagy induced by Fk506 also lead to high-mobility group box(HMGB)1 release from nuclei,resulting in hepatocyte injury through triggering of p38 phosphorylation and chemokine release.Iso effectively inhibited the release of HMGB 1 and downstream inflammatory cytokines.Conclusions:Iso could inhibit release of HMGB1 by Fk506 and enhance the hepatoprotective effect of Fk506 in rat liver transplantation.Combining Iso with Fk506 would be a promising strategy for the patients after liver transplantation.Part 2 Isoglycyrrhizinate Magnesium decreases the risk ofbiliary complications after liver transplantation:a retrospectivecohort studyAbstractBackground:Ischemia-reperfusion injury after liver transplantation(LT)impairs graft function and affects prognosis of recipients.Compounds derived from licorice root were believed to be hepatoprotective and usually used after liver injury.In this study,we intended to compare the protective effect of Isoglycyrrhizinate magnesium(Iso)and Glycyrrhizin(Gly)after liver transplantation.Methods:All patients received liver transplantations from Jan 1st 2015 to Dec 31st 2015 at First affiliated hospital of Zhejiang University were included in this study.124 patients were treated with Iso as well as 34 patients treated with Gly.Clinical data and surviving information were collected for further statistical analysis.Results:Of all the patients included in this study,Iso and Gly showed similar effect in 1 year overall survival after liver transplantation.In analyzing death within 1 month after liver transplantation,no significant differences were noticed between Iso and Gly.We also found no disparities in vascular complications between two treatments.However,compared to Gly,Iso treatment significantly decreased the risk of developing biliary complications(15%vs 29%,p<0.05).The concentration of Fk506 14 days after LT was elevated with Iso treatment compared to Gly.Conclusions:The risk of developing biliary complications after liver transplantation was decreased when treated with Isoglycyrrhizinate Magnesium.However,prospective study and blank control group are needed.