2008•Journal of Sun Yat-sen UniversityRequires access
Pattern of Early Intragraft Cytokines Following Rat Partial Liver Transplantation
Chen Gui-hua, Sun Yat-sen
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Abstract
[Objective] To explore the effect of different cold ischemia (CI) times on the patterns of intragraft cytokines of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and their correlation with regeneration after rat partial liver transplantation. [Method] Model of Lewis rat 50% partial liver transplantation (LT) was established. The rats were divided into 3 groups: group of 1 h CI (20 cases), group of 8 h CI (20 cases) and group of 16 h CI (20 cases). Survival rate of each group was recorded. Specimens were collected at predetermined intervals from 90 min, 1, 2, 4, and 7 d post-reperfusion. Expression pattern of TNF-α and IL-6 were determined in liver grafts with different CI times following transplantation. Progression of DNA synthesis of hepatocyte was confirmed by bromodeoxyuridine (BrdU) uptake. [Results] A total of 60 Partial LTs were performed and operative success rate of partial LT was 100% in all groups. Survival in groups with 1 h and 8 h CI was 100% ( 7 d). Survival in group with 16 h CI was 20% ( 7 d). Compared with 1 h CI, IL-6 and TNF-α expression in partial liver grafts preserved for 8 h and 16 h were markedly increased post-transplantation (P 0.05). Positively BrdU-stained neclei were quantitated and analyzed between experimental groups. Number of positively stained neclei in 8 h CI group were more than those in 1 h CI groups at 24 h after transplantation (P 0.05), indicating the initiated and completed cell cycle progression and liver regeneration. At 24 h after transplantation, BrdU uptake was minimal in the rat livers with 16 h cold ischemia. [Conclusion] Upregulation of cytokines of TNF-α and IL-6 is an important factor in initiating and completing early partial liver graft regeneration. Mild (1 h) and moderate (8 h) CI could initiate and complete liver regeneration after rat partial LT, but partial grafts with severe CI (16 h) fail to achieve liver regeneration despite the presence of early initiating signals.