2000•Zhongguo bingli shengli zazhiRequires access
Molecular mechanisms of liver regeneration following cold ischemia injury after liver transplantation in rat
Wang Guodong, Yi Ma, Chen Gui-hua
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Abstract
AIM:To study the molecular mechanisms of liver regeneration following different cold ischemia(CI)times after liver transplantation in a rat model.METHODS:A model of rat orthotopic liver transplantation was established.The rats were divided into 3 groups:1 h CI group,8 h CI group and 16 h CI group.Survival rate in each group was recorded.Specimen were collected at predetermined intervals from 90 min,1,4 and 7 d post-reperfusion.The patterns of TNF-α,IL-6 and STAT3 activation were determined in liver grafts with 1 h,8 h and 16 h CI times.Expression of cyclin D1 and hepatocyte replication with bromodeoxyuridine(BrdU)were confirmed by immunohistochemistry.The results of TNF-α and IL-6 expression in all groups were analyzed after whole liver transplantation.Statistical analysis was used to compare BrdU positively stained hepatocytes at 48 h post-reperfusion.RESULTS:Liver transplantation was successfully performed in all experimental groups.Survival rate in each group was 100%(14 d).Compared with 1 h CI,TNF-α expressions in whole liver grafts with 8 h and 16 h CI were markedly increased at 90 min after reperfusion(P0.05).Compared with 1 and 8 h CI,IL-6 expression in liver grafts preserved for 16 h were markedly increased at 90 min after transplantation(P0.05).With 8 and 16 h CI,STAT3 activity was markedly increased.Cyclin D1 expression in 8 CI group was demonstrated with cytoplasmic and nuclear staining at 24 h in liver grafts.Cyclin D1 expression was mainly nuclear in 16 h CI group.Extensive hepatocyte replication was present.The numbers of hepatocytes with positively stained nuclei in 16 h CI group were more than those in 1 and 8 h CI group at 48 h after transplantation(P0.05).CONCLUSION:Rat whole liver grafts with 16 h CI injury still initiate and complete liver regeneration and graft recovery after liver transplantation.Liver regeneration following transplantation may be through TNF-α/IL-6/STAT3/cyclin D1/DNA synthesis pathways.