Changes of early intragraft cytokines following small-for-size liver transplantation in rats

Abstract

Objective To explore the effect of different cold ischemia (CI) time on the changes of early intragraft cytokines (TNF-α and IL-6) and their correlation with regeneration after small-for-size (30% standard volume) liver transplantation (LT) in rats. Methods A model of Lewis rat 30% standard volume liver transplantation was established. The rats were divided into 3 groups: 1 h CI group, 8 h CI group and 16 h CI group (n= 20 in each group) according to the CI time of donor livers stored in UW solution. Survival rate at day 7 after LT in each group was recorded and specimens were collected at predetermined intervals from 90 min, 1, 2, 4 h and 7 day post-reperfusion. Expression patterns of TNF-αand IL-6 were determined and compared in 30% liver grafts with different CI time following transplantation. Progression of DNA synthesis of hepatocytes was confirmed by BrdU uptake. Morphological assessment of the liver grafts was also made. Results Operative success rate of LT was 100% in all groups. Mean survival rate in 1 h and 8 h CI group was 100% respectively (＞ 7 day). Mean survival rate in 16 h CI group was low, and no recipient animals survived on the postoperative day 7. Compared with 1 h CI group, IL-6 expression in 30% liver grafts stored for 8 h and 16 h was markedly increased post-transplantation (F=184.12, P<0.05). TNF-α expression in 30% liver grafts in 8 h and 16 h CI groups was markedly increased post-reperfusion (F=58.81, P< 0.05). There was no statistically significant difference in the expression of TNF-α and IL-6 between 8 h CI and 16 h CI groups. Number of positively stained nuclei in 1 h CI group was greater than that in 8 h CI group at 24 h after transplantation (t=5.59, P<0.05). At 24 h after transplantation histology showed mild injury in grafts of CI 1 h group. CI 8 h led to mild sinusoidal dilatation and inflammation.Grafts stored for 16 h demonstrated focal congestion, hepatocyte collapse and necrosis. Conclusion At the early stage of small-for-size liver transplantation, up-regulation of cytokines (TNF-α and IL-6) is an important factor in the liver regeneration. The early initiating signals for the regenerative response are present in the small-for-size liver grafts with different CI time. Key words: Ischemia; Organ preservation; Liver transplantation; Interleukin-6; Tumor necrosisfactor-alpha