Adenoviral cardiotrophin‐1 transfer improves survival and early graft function after ischemia and reperfusion in rat small‐for‐size liver transplantation model
Adenoviral cardiotrophin‐1 transfer improves survival and early graft function after ischemia and reperfusion in rat small‐for‐size liver transplantation model
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DOI：
10.1111/j.1432-2277.2007.00616.x
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发表时间：
2008-04
影响因子：
3.1
通讯作者：
Jun Song;Ye-wei Zhang;A. Yao;Yue Yu;Z. Hua;Liyong Pu;Guo-qiang Li;Xiang-Cheng Li;Feng Zhang;Guo-qing Sheng;Xuehao Wang
中科院分区：
文献类型：
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作者：
Jun Song;Ye-wei Zhang;A. Yao;Yue Yu;Z. Hua;Liyong Pu;Guo-qiang Li;Xiang-Cheng Li;Feng Zhang;Guo-qing Sheng;Xuehao Wang
本研究旨在探讨供体肝腺病毒心肌营养素-1(CT-1)基因转移对大鼠小体积肝移植早期移植物存活和功能的影响。我们构建了重组小鼠CT-1腺病毒载体。用表达CT-1的腺病毒(AdCT-1)或对照载体(AdEGFP)体内转导供体大鼠。4天后取肝脏，减至体重的40%，然后移植。同种异体大鼠原位肝移植模型采用40%的小体积移植物。评估移植物存活率、肝功能、肝脏结构改变、坏死和凋亡程度，以及细胞存活信号通路。AdCT-1预处理可明显改善小体积移植物的存活率和肝功能。CT-1治疗组移植后肝脏结构得到较好保护，凋亡和坏死细胞减少，抗凋亡蛋白bcl2表达上调，促凋亡裂解caspase-3表达下调，蛋白激酶B(Akt)、细胞外调节激酶(ERK)和信号转导与转录激活因子-3(Stat-3)的磷酸化激活了细胞存活信号通路。结论：供体肝腺病毒CT-1通过激活Akt、ERK和Stat-3生存信号通路，减少小体积肝移植的肝坏死和细胞凋亡，从而减轻缺血/再灌注损伤。这些结果可能为改善小体积肝移植的预后提供一种潜在的临床策略。
This study was to investigate the effect of donor liver adenoviral cardiotrophin‐1 (CT‐1) gene transfer on early graft survival and function in rat small‐for‐size liver transplantation. We constructed a recombinant murine CT‐1 adenoviral vector. Donor rats were transduced in vivo with adenoviruses expressing CT‐1 (AdCT‐1) or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40% of weight, and transplanted. A syngeneic rat orthotopic liver transplantation model was performed using 40% small‐for‐size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cell survival signaling pathways were assessed. AdCT‐1 pretreatment markedly improved liver function and the survival of small‐for‐size grafts. In the CT‐1 treatment group, hepatic architecture was well protected, apoptotic and necrotic cells were reduced; anti‐apoptotic protein bcl‐2 was up‐regulated and pro‐apoptotic cleaved caspase‐3 was down‐regulated, cell survival signaling pathways were activated by phosphorylation of protein kinase B (Akt), extracellular‐regulated kinase (ERK) and Signal transducer and activator of transcription‐3 (Stat‐3) after transplantation. In conclusion, donor liver adenoviral CT‐1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosis in small‐for‐size liver transplantation, mediated in part by activation of the Akt, ERK, and Stat‐3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small‐for‐size liver grafts.