Orthotopic liver transplantation from cardiac death donors in the mouse: a new model and evaluation of cardiac death time.

Orthotopic liver transplantation from cardiac death donors in the mouse: a new model and evaluation of cardiac death time.
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小鼠心脏死亡供体原位肝移植:心脏死亡时间的新模型和评估

DOI:
10.22038/ijbms.2017.8838
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发表时间:
2017-06
影响因子:
2.2
通讯作者:
Liu Q
Liu Q
中科院分区:
医学4区
文献类型:
--
作者:
Liu Z;Pan N;Lv X;Li S;Wang L;Liu Q

文献摘要

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目的:本研究的目的是建立一种小鼠心脏死亡后供体原位肝移植模型。材料与方法:将小鼠随机分为实验组和假手术组。实验组小鼠根据供肝热缺血时间(WIT)分为3组:正常LTx组、WIT 30 min +LTx组和WIT 45 min +LTx组。使用微型主动脉夹夹闭降主动脉,以模拟DCD移植物中的心脏骤停。随后,将移植物原位移植到C57 BL/6小鼠中。观察7 d存活率、血清丙氨酸氨基转移酶(ALT)、诱导型一氧化氮合酶(iNOS)、白细胞介素6(IL-6)mRNA水平、肿瘤坏死因子α(TNF-α)mRNA水平及肝脏病理学改变。结果如下:WIT 45 min+LTx组的7天生存率明显低于正常LTx组(25% vs100%,P值<0.05),而WIT 30 min +LTx组与正常LTx组的7天生存率无显著差异(75% vs100%,P值>0.05)。WIT 45 min+LTx组血清ALT水平明显高于正常LTx组和WIT 30 min+LTx组(P <0.01)。三组间的坏死和凋亡差异有统计学意义(P值<0.05)。WIT 45 min +LTx组iNOS、IL-6 mRNA和TNF-α mRNA表达均较正常LTx组和WIT 30 min+ LTx组显著升高。结论:本实验建立的小鼠DCD LTx模型是可行的,为DCD移植物LTx的生物医学研究提供了有利条件。
Objective(s): The goal of this research was to develop a mouse orthotopic liver transplantation (LTx) model from donor-after-cardiac-death (DCD) grafts. Materials and Methods: Mice were randomly assigned to the experimental group or the sham group. The mice in the experimental group were divided into three groups according to the warm ischemia time (WIT) of liver graft: normal LTx, WIT 30 minute (min) +LTx and WIT 45 min +LTx. The descending aorta was clamped using a miniature aortic clamp to simulate cardiac arrest in the DCD grafts. Subsequently, the grafts were orthotopically transplanted into C57BL/6 mice. The 7-day survival rate, serum alanine aminotransferase (ALT), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) mRNA level, tumor necrosis factor-alpha (TNF-α) mRNA level, as well as hepatic pathologic alterations were observed. Results: The 7-day survival rate was markedly lower in the WIT 45 min+LTx group than that in the normal LTx group (25% versus 100%, P-value<0.05), with no significant difference between the WIT 30 min +LTx and normal LTx group (75% versus 100%, P-value>0.05). Serum ALT level of WIT 45 min+LTx group was markedly higher than that of normal LTx and WIT 30 min+LTx group (P-value<0.01). There were significant differences in necrosis and apoptosis among the three groups (P-value<0.05). The expression of iNOS, IL-6 mRNA and TNF-α mRNA in WIT 45 min +LTx group all increased significantly compared with the normal LTx and WIT 30 min+LTx group. Conclusion: The DCD LTx model is feasible in the mouse and would provide many advantages for biomedical research on LTx from DCD grafts.