Objective ::To investigate the role of trehalose in hepatic ischemia-reperfusion injury and its underlying mechanisms.Methods:C57BL/6J mice were randomly divided into no-ischemia group, ischemia-reperfusion group, trehalose-treated group and normal saline control group. After ischemia for 90 minutes, reperfusion immediately or 6h, blood and liver tissues were collected, and serum was separated. The liver function parameters of ALT, AST, the inflammatory factors of TNF-α, IL-1β and IL-2, and the pathological changes of liver were detected to study the role of trehalose during hepatic ischemia-reperfusion injury. Hypoxia-reoxygenation cell model was established by AML12 mouse hepatocyte line, and divided into experimental group and control group. The experimental group was divided into low dose group and high dose group according to the concentration of trehalose administrated. And the control group had no use of trehalose. The level of apoptosis was measured to study the effect of trehalose on apoptosis induced by hepatic ischemia-reperfusion injury with flow cytometry. Western blot was utilized for detecting the levels of Caspase-3, Cleaved Caspase-3 and Bcl-2 protein to understand the molecular mechanisms of trehalose in apoptosis during hepatic ischemia-reperfusion injury.Results:In vivo animal experiments showed that liver function and such inflammatory factors as ALT, AST, TNF-α, IL-1β and IL-2 increased in ischemia-reperfusion group after hepatic ischemia-reperfusion ( P<0.05), and liver tissue became necrotic. After a treatment of trehalose, the levels of ALT, AST, TNF-α, IL-1β and IL-2 were lower than those of normalsaline control group and the area of liver tissue necrosis also decreased ( P<0.05). In vitro cell experiments showed that the apoptosis level of hepatocytes in the experimental group decreased compared with the control group.And the level of activated pro-apoptotic protein Cleaved Caspase-3 decreased, the level of anti-apoptotic protein Bcl-2 increased. Conclusions:Trehalose has protective effects on hepatic ischemia-reperfusion injury in vivo and in vitro. The mechanism may be involved in inhibiting inflammation induced by hepatic ischemia-reperfusion injury, suppressing the activation of Caspase-3 and promoting the expression of Bcl-2, thus played a protective role by extenuation of hepatocyteapoptosis.

Objective:To explore the impact of donor cold ischemia time(CIT)on early recovery after liver transplantation(LT).Methods:From January 2016 to December 2020, the relevant clinical data were retrospectively reviewed for 456 LT recipients.According to the value of CIT of donor liver, they were assigned into two groups of CIT >5 h and CIT≤5 h. T, Mann-Whitney U or Chi square test was employed for statistical processing.Intraoperative findings and liver function(LF)parameters of two groups were compared, including operative duration, intraoperative volume of hemorrhage, erythrocyte transfusion and anhepatic phase.LF parameters included alanine aminotransferase(ALT), aspartate aminotransferase(AST)and total bilirubin(TB)within Day 1-7 post-LT.Postoperative recovery was evaluated by postoperative stay of intensive care unit(ICU), normalization time of liver function recovery, length of postoperative hospitalization and incidence of postoperative complications.Results:Among them, 407(89.3%)patients underwent classic orthotopic LT.Median CIT of donor liver was 309 min.In CIT≤5 h and CIT >5 h groups, operative duration was[(446.3+ 76.8)vs.(526.0+ 98.1)min], anhepatic phase time[(51.9+ 13.3)vs.(62.6+ 18.9)min]and intraoperative volume of erythrocyte transfusion[(7.3+ 5.8)vs.(10.0+ 6.87)U]. And the differences were statistically significant( P<0.001, 0.001 & 0.001). Postoperative hospitalization stay was longer[(29.1±15.9)vs.(27.1±13.0)]day.And the incidence of postoperative complications was higher in CIT >5 h group[22.7%(54/238)vs.12.4%(27/218)]. And the difference was statistically significant( P=0.045 & 0.004). As compared with CIT≤5 h group, ALT, AST & TB spiked in CIT >5 h group at Day 1 post-operation and the differences were statistically significant( P=0.002, P<0.001, P=0.001). In CIT >5 h group, ALT rose at Day 2/5/6/7 post-LT( P=0.026, 0.026, 0.015 & 0.011), AST jumped from Days 2-6( P=0.002, 0.004, 0.035, 0.029 and 0.019)and TB increased from Days 2-7 post-LT and the differences were statistically significant( P=0.003, 0.014, 0.030, 0.039, 0.027 & 0.009). LF recovered at CIT≤5 h and CIT>5 h group[(10.0±3.2)vs.(10.7±3.3)day]. There were significantly statistical differences( P=0.044). Conclusions:Non-conducive to patient recovery, prolonged cold ischemic time aggravates early LF injury post-LT.