Liang Ting-Bo, Man Kwan, Kin-Wah Lee Terence, Hong-Teng Tsui Steven, Lo Chung-Mau, Xu Xiao, Zheng Shu-Sen, Fan Sheung-Tat, Wong John
Centre for the Study of Liver Disease, The University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong SAR, China.
Transplantation. 2003 Mar 15;75(5):673-8. doi: 10.1097/01.TP.0000048490.24429.89.
The molecular mechanism of small-for-size graft injury remains unclear. The aim of this study is to investigate the gene expression pattern of acute phase response in relation to graft size in a rat-liver transplantation model.
A rat orthotopic liver transplantation model using 30%, 50%, and whole grafts was used. The graft survival rates and liver morphology were compared among the three groups. Two transcription factors, nuclear factor (NF)-kappaB (p65) and early growth response (Egr-1), and their downstream genes were compared.
According to the graft size, the rats were grouped as follows: group 1 (n=20), 32% (24-47%); group 2 (n=10), 56% (50-65%); and group 3 (n=10), 104% (89-120%). The 7-day survival rates were 20% (P=0.039 vs. group 2, P=0.000 vs. group 3), 60%, and 100% in groups 1, 2, and 3, respectively. Dilation of hepatic sinusoids and vacuolization of hepatocytes were observed in group 1. Up-regulation of Egr-1 and endothelin (ET)-1 and over-expression of nitric oxide synthase (iNOS) was found in group 1, but heme oxygenase (HO)-1 and A20 were down-regulated. At 24 hours after reperfusion, the intragraft protein level of heat-shock protein (Hsp)-70 was significantly lower in group 1 than that in group 3 (12.4 vs. 17.0 ng/mL, P=0.04). More apoptotic nuclei were found in group 1.
Small-for-size graft injury was related to early over-expression of Egr-1 associated with up-regulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.
小体积移植肝损伤的分子机制仍不清楚。本研究旨在探讨大鼠肝移植模型中与移植肝大小相关的急性期反应的基因表达模式。
采用大鼠原位肝移植模型，分别移植30%、50%体积的肝脏以及全肝。比较三组的移植肝存活率和肝脏形态。比较两种转录因子，即核因子（NF）-κB（p65）和早期生长反应因子（Egr-1）及其下游基因。
根据移植肝大小，将大鼠分为以下几组：第1组（n = 20），32%（24 - 47%）；第2组（n = 10），56%（50 - 65%）；第3组（n = 10），104%（89 - 120%）。第1、2、3组的7天存活率分别为20%（与第2组相比，P = 0.039；与第3组相比，P = 0.000）、60%和100%。在第1组中观察到肝血窦扩张和肝细胞空泡化。第1组中发现Egr-1和内皮素（ET）-1上调，一氧化氮合酶（iNOS）过度表达，但血红素加氧酶（HO）-1和A20下调。再灌注后24小时，第1组移植肝内热休克蛋白（Hsp）-70的蛋白水平显著低于第3组（12.4对17.0 ng/mL，P = 0.04）。第1组中发现更多凋亡核。
小体积移植肝损伤与Egr-1早期过度表达有关，Egr-1过度表达与ET-1上调以及热休克蛋白和A20下调所反映的细胞内稳态恶化有关。
