| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Background and aim : We investigated the chronological profile of graft damage and recovery after liver cold ischemia-reperfusion (I/R) injury, paying particular attention to the role of apoptosis on hepatocyte and sinusoidal endothelial cell (SEC) damage. Methods : Male Lewis rats underwent re-arterialized orthotopic liver transplantation (OLT) using grafts subjected to a short period (UW1h) and to prolonged (UW16h) cold preservation. Experiments were performed immediately after preservation, 4h, 24h, 3days and 7days after reperfusion. At each time point, graft function, the incidence of apoptotic cells, expression of the epitope recognized by SEHL (a monoclonal antibody specific to rat SECs) and the incidence of proliferating cells was estimated. Results: In the UW16h group, the proportion of apoptotic SECs was markedly elevated at 4h. The incidence of hepatocyte apoptosis was very low, although massive hepatocyte necrosis was evident at 24h. The incidence of proliferating hepatocytes and SECs peaked at 3days and then returned to normal by 7days. Expression of SE-1was reduced immediately after preservation, followed by a marked reduction at 4h and 24h after reperfusion and then expression returned to normal by 7days. Conclusion : While SEC apoptosis was induced in the early phase of cold I/R injury, hepatocyte damage developed without the occurrence of apoptosis. Regeneration of both hepatocytes and SECs following cold I/R injury peaked 3days and was complete by 7days, whereas functional recovery of these cell populations was complete 3days after reperfusion.
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