A study on the mechanisms involved in early liver graft regeneration following cold ischemia in a rat liver transplantation model / 中华普通外科杂志

ABSTRACT

Objective To study the molecular mechanism involved in early liver regeneration following cold ischemia after rat orthotopic liver transplantation(OLT). Methods Syngeneic(Lewis to Lewis)rat OLT with hepatic artery reconstruction was performed.Graft survival and liver regeneration following 1 h and 16 h cold ischemic injury were evaluated.Specimen were collected at predetermined intervals from 0,1,2,4,16,24,48,72 h post-reperfusion.The patterns of IL-6 and TNF-α expression,STAT3 activation,and upregulation of immediately early genes(IEGs)including c-fos,c-myc,and c-jun were determined in liver grafts with 1 h and 16 h cold ischemia times.Quantitative analysis of IL-6 at 2 h after reperfusion was performed for grafts preserved for 1 h and 16 h.Progression of hepatocyte replication was confirmed by bromodeoxyuridine(BrdU)immunohistochemistry.Positively BrdU-stained nuclei were quantitated and analyzed between the two groups at 48 h after reperfusion. Results Survival rate in the two groups was 100%.Compared to 1 h cold ischemia group,IL-6 and TNF-α expression and STAT3 activation in 16 h cold ischemia group were markedly increased.Extensive hepatocyte replication was present.Upregulation of immediate early genes of c-fos,c-myc,and c-jun was also observed.Grafts with 1 h ischemic iniury had lower levels of IL-6 than that when grafts suffering from ischemia for 16 h(t=27.7,P＜0.05).Number of positively stained nuclei in 16 h group were more than that in 1 h group at 48 h after transplantation(t=13.4,P＜0.05). Conclusions Severe cold ischemia initiated liver regeneration after rat OLT.TNF-α and IL-6 are important factors in early liver regeneration.IL-6/STA3 pathway in liver regeneration is an important part in the recovery of grafts following cold ischemia injury.