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肝动脉重建可预防大鼠肝移植中移植物的缺血性损伤,抑制移植物排斥反应,并介导移植物的长期存活。

Hepatic artery reconstruction prevents ischemic graft injury, inhibits graft rejection, and mediates long-term graft acceptance in rat liver transplantation.

作者信息

Ishii E, Shimizu A, Kuwahara N, Kanzaki G, Higo S, Kajimoto Y, Arai T, Nagasaka S, Masuda Y, Fukuda Y

机构信息

Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.

出版信息

Transplant Proc. 2013 Jun;45(5):1748-53. doi: 10.1016/j.transproceed.2013.01.086.

DOI:10.1016/j.transproceed.2013.01.086
PMID:23769037
Abstract

BACKGROUND

Hepatic artery (HA) reconstruction is performed in the clinical liver transplantation.

METHODS

We assessed the importance of HA reconstruction in the success of liver transplantation. Orthotopic liver transplantation was performed without immunosspression from Lewis (RT1l) to Lewis rats (syngeneic transplantation) as well as Lewis to BN (RT1n) rats (allogeneic transplantation) with or without HA reconstruction. We examined graft function, pathology, and mRNA levels using DNA arrays in both arterialized and nonarterialized liver grafts.

RESULTS

In Lewis-to-Lewis syngeneic grafts, both the arterialized and nonarterialized grafts survived >120 days with normal graft function. lnfiltration of CD3(+) T cells and CD68(+) macrophages, marked bile duct proliferation with apoptotic epithelial cells, and expansion and increasing fibrosis of portal areas were evident in the nonarterialized grafts at day 120, although preservation of architecture was noted in the arterialized grafts. DNA array analysis of nonarterialized syngeneic grafts demonstrated the upregulation of mRNA of cell death-related proteins, cell cycle-related proteins, and inflammation-related proteins than those in arterialized grafts. Moreover, the arterialized Lewis-to-BN allogeneic grafts could survive for a long time with less severe graft dysfunction than those in non-arterialized allogeneic grafts.

CONCLUSIONS

HA reconstruction in liver transplantation inhibited hypoxic injury and subsequent inflammation and bile duct proliferation, prevented the augmentation of T-cell-and antibody-mediated rejection, and mediated long-term graft acceptance. HA reconstruction is essential factor in the success of liver transplantation.

摘要

背景

肝动脉(HA)重建在临床肝移植中得以实施。

方法

我们评估了HA重建对肝移植成功的重要性。在不进行免疫抑制的情况下,将肝脏从Lewis(RT1l)大鼠原位移植到Lewis大鼠(同基因移植)以及从Lewis大鼠移植到BN(RT1n)大鼠(异基因移植),分别进行有或无HA重建的操作。我们使用DNA芯片检测了动脉化和非动脉化肝移植物的移植物功能、病理情况以及mRNA水平。

结果

在Lewis到Lewis的同基因移植物中,动脉化和非动脉化移植物均存活超过120天,且移植物功能正常。在第120天时,非动脉化移植物中可见CD3(+) T细胞和CD68(+)巨噬细胞浸润,胆管明显增生并伴有凋亡上皮细胞,门管区扩张且纤维化增加,尽管动脉化移植物的结构得以保留。非动脉化同基因移植物的DNA芯片分析显示,与动脉化移植物相比,细胞死亡相关蛋白、细胞周期相关蛋白和炎症相关蛋白的mRNA上调。此外,动脉化的Lewis到BN异基因移植物能够长期存活,与非动脉化异基因移植物相比,移植物功能障碍较轻。

结论

肝移植中的HA重建可抑制缺氧损伤及随后的炎症和胆管增生,防止T细胞和抗体介导的排斥反应增强,并介导移植物的长期存活。HA重建是肝移植成功的关键因素。

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1
Hepatic artery reconstruction prevents ischemic graft injury, inhibits graft rejection, and mediates long-term graft acceptance in rat liver transplantation.肝动脉重建可预防大鼠肝移植中移植物的缺血性损伤,抑制移植物排斥反应,并介导移植物的长期存活。
Transplant Proc. 2013 Jun;45(5):1748-53. doi: 10.1016/j.transproceed.2013.01.086.
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Chronic antibody-mediated responses may mediate chronic rejection in rat orthotopic liver transplantation.慢性抗体介导的反应可能介导大鼠原位肝移植中的慢性排斥反应。
Transplant Proc. 2013 Jun;45(5):1743-7. doi: 10.1016/j.transproceed.2013.02.045.
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The value of hepatic artery reconstruction as a technique in rat liver transplantation.肝动脉重建作为大鼠肝移植技术的价值。
Surgery. 1992 Feb;111(2):195-200.
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Persistence of impaired hepatic microcirculation after nonarterialized liver transplantation in the rat.大鼠非动脉化肝移植后肝微循环障碍的持续存在。
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The dynamic changes of T-bet(+)/GATA-3(+) and RORgammat(+)/FOXP3(+) cells in recipient spleens and grafts after rat orthotopic liver transplantation.大鼠原位肝移植后受体脾脏和移植物中 T-bet(+) / GATA-3(+)和 RORgammat(+) / FOXP3(+)细胞的动态变化。
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