大鼠30%体积肝脏移植后肝脏再生的分子机制

Liver regeneration after 30% rat liver transplantation

Objective To explore the molecular mechanisms involved in liver regeneration after different cold ischemic (CI) times for the liver graft in 30% volume rat liver transplantation. Methods A model of 30% volume Lewis to lewis rat liver transplantation with hepatic artery reconstruction was established. Rats were grouped as follows: 1 h CI group (n =25), 8 h CI group (n =25) and 16h CI group (n = 25). Survival rate of rats in each group and liver regeneration were observed. Specimen were collected at predetermined intervals from 90 min, 1,4 and 7 d post-reperfusion. TNF-α and IL-6 expression, STAT3 activation were determined in liver grafts. Expression of cyclin D1 and hepatocyte replication with BrdU uptake were studied by immunohiatochemistry. Statistical analysis was used to compare BrdU positively stained hepatoeytes at 1 d post- reperfusion in each group. Results 30% liver transplantation was performed in a total of 75 rats. Compared with rats in 1 h CI group, TNF-α and IL-6 expression in 8 h CI and 16 h CI groups were markedly increased after 30% liver transplantation. STAT3 activity in 8 h CI and 16 h CI groups was significantly increased. Cyclin D1 expression in 8 CI group was demonstrated with cytoplasmic and nuclear staining. Grafts in 16 h CI group showed large areas with no cyclin D1 expression. Number of hepatoeytes with positively stained neclei in 1 h CI group was more than that in 8 h CI group at 1 d after transplantation (t = 6.14, P < 0.05). Conclusion Liver regeneration following 30% liver graft transplantation may be through TNF-α/IL-6/STAT3/ Cyclin D1/DNA synthesis pathways. The reason for 30% liver graft failure with significant cold ischemic injury is that hepatocytes may not respond to initiating signals for liver graft regeneration.