Distinct intragraft response pattern in relation to graft size in liver transplantation
Distinct intragraft response pattern in relation to graft size in liver transplantation
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DOI：
10.1097/01.tp.0000048490.24429.89
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发表时间：
2003-03-15
期刊：
影响因子：
6.2
通讯作者：
Wong, J
中科院分区：
文献类型：
--
作者：
Liang, TB;Man, K;Wong, J
背景小尺寸移植物损伤的分子机制仍不清楚。本研究的目的是研究大鼠肝移植模型中急性期反应的基因表达模式与移植物大小的关系。采用30%、50%和全肝移植的大鼠原位肝移植模型。比较三组间移植物存活率及肝脏形态学变化。比较两种转录因子NF-κ B（p65）和早期生长反应（Egr-1）及其下游基因。根据移植物大小，将大鼠分组如下：组1（n=20），32%（24-47%）;组2（n=10），56%（50-65%）;组3（n=10），104%（89-120%）。第1、2和3组的7天生存率分别为20%（与第2组相比P =0.039，与第3组相比P=0.000）、60%和100%。第1组肝窦扩张，肝细胞空泡化。第1组Egr-1、ET-1表达上调，一氧化氮合酶（iNOS）表达上调，血红素氧合酶（HO）-1、A20表达下调。再灌注后24 h，移植肾内热休克蛋白（Hsp）-70水平1组明显低于3组（12.4 vs.17.0 ng/mL，P=0.04）。第1组凋亡细胞核增多。小尺寸移植物损伤与Egr-1的早期过度表达相关，Egr-1与ET-1的上调和Hsps和A20的下调所反映的细胞内稳态的恶化相关。
Background. 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.Methods. 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.Results. 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.Conclusions. Small-for-size graft injury was related to early over-expression of Egr-1 associated with upregulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.