Effects of hypoxia inducible factor-1α with high expression mediated by hypoxia precondition on the JNK signaling pathway in rats received orthotopic liver autotransplantation / 中华消化外科杂志

ABSTRACT

Objective To investigate the expression of hypoxia inducible factor-1α(HIF-1α)in the transplanted liver in rats and the role of HIF-1α in the JNK signaling pathway.Methods Ninety-six SD rats were randomly divided into normal control(NC)group,autotransplantation(AT)group,hypoxia preconditioning (HP)+ AT group according to simple random sampling method.No treatment was applied to the rats in the NC group except for blood vessel separation.Stable rat models of 70％ AT was established in the AT group.Rats in the HP + AT group were given 8％ oxygen mixed gas for 90 minutes before the operation.The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected at 1,2,12,24 hours after operation,and the expression of HIF-1α in the hepatic tissue,mRNA expression of c-Jun,and protein expression of Cleaved Caspase-3 were detected by immunohistochemical staining,reverse transcription-polymerase chain reaction and Western blot,respectively.All data were analyzed using the analysis of variance or t test.Results The levels of ALT and AST in the HP + AT group were significantly lower than those in the AT group,while higher than those in the NC group at 1,2,12 and 24 hours after the operation(F=2631.371,1177.642,810.383,682.848;743.618,1095.522,375.995,580.613,P ＜0.05).The protein expression levels of HIF-1α in the AT group were significantly lower than those in the HP + AT group,but higher than those in the NC group at 1,2,12 and 24 hours after operation(F = 191.737,284.482,459.419,213.782,P ＜ 0.05).The mRNA expression levels of c-Jun in the HP + AT group were significantly lower than those in the AT group,while higher than those in the NC group at 1,2 and 12 hours after operation(F = 66.211,53.169,9.645,P ＜ 0.05).There was no significant difference in the mRNA expression of c-Jun among the 3 groups at 24 hours after operation(F = 1.100,P ＞ 0.05).The protein expressions of Cleaved Caspase-3 in the HP + AT group were significantly lower than those in the AT group,while higher than those in the NC group at 1,2,12 and 24 hours after the operation(F =23.133,31.158,14.347,29.043,P ＜ 0.05).Conclusion High expression of HIF-1α after HP inhibits apoptosis of hepatic cells and alleviates ischemia reperfusion injury of hepatic tissues by suppressing JNK activation,down-regulating protein expression of Cleaved Caspase-3 after orthotopic liver transplantation in rats.