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 role and molecular mechanism of DNAJB6 in liver regeneration during partial liver transplantation(PLT).Methods:Dark agouti(DA, donor)and Lewis(recipient)rats were prepared for liver regeneration model of PLT.Rats were divided into before perfusion, after split liver perfusion, after portal vein opening, before abdominal closure and Day 3/7 after surgery groups(n=6 each)for timepoints of PLT.C57 mice were performed for residual liver regeneration model of partial hepatectomy and divided into control, Day 1/2/3/4/5 groups(n=6 each)for timepoints of hepatectomy.Gene Expression Omnibus liver regeneration data were utilized for locating DNAJB6 in liver regeneration.DNAJB6 low-expression human hepatocytes were constructed by DNAJB6-Si transfection.The relationship between DNAJB6 and liver regeneration was examined by Western blot detection of cell proliferation markers PCNA and CCK8 cell proliferation experiments.And the possible molecular mechanism of DNAJB6 regulating liver regeneration in PLT was studied by Western blot detection of nuclear protein and protein in cell proliferation signal pathway.Results:The result of residual liver regeneration of partial hepatectomy showed that DNAJ family genes were differentially expressed on regenerated liver gene chip and DNAJB6 was lowly expressed on regenerated liver gene chip.Meanwhile, DNAJB6 was lowly expressed in regenerated liver tissues of PLT and partial liver resection.After silencing DNAJB6 by transfecting DNAJB6-Si, the cellular expression level of PCNA and proliferation rate increased.However, nuclear extraction failed to detect the nuclear/plasma changes of β-catenin and the level of Wnt4 protein had no obvious change.Although the activation levels of p38 and JNK2 downstream of Ras/MAPK showed no change, there was a higher activation level of ERK.Conclusions:In regenerating liver tissue, hepatocytes may suppress the Ras/MEK/ERK signaling pathway by lowering the expression level of DNAJB6 to promote liver regeneration.