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异种肝移植术后组织因子激活介导受体凝血功能障碍的机制

吴恩昊 李霄 陶开山

吴恩昊, 李霄, 陶开山. 异种肝移植术后组织因子激活介导受体凝血功能障碍的机制[J]. 器官移植, 2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002
引用本文: 吴恩昊, 李霄, 陶开山. 异种肝移植术后组织因子激活介导受体凝血功能障碍的机制[J]. 器官移植, 2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002
Wu Enhao, Li Xiao, Tao Kaishan. Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002
Citation: Wu Enhao, Li Xiao, Tao Kaishan. Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 174-180. doi: 10.3969/j.issn.1674-7445.2018.03.002

异种肝移植术后组织因子激活介导受体凝血功能障碍的机制

doi: 10.3969/j.issn.1674-7445.2018.03.002
基金项目: 

国家“973”计划 2015CB554100

国家重点研发计划 2017YFC1103700

国家“863”计划 2012AA021005

国家自然科学基金 81300361

国家自然科学基金 81270549

国家自然科学基金 81470873

国家自然科学基金 81671838

国家自然科学基金 81670593

西京医院学科助推计划 XJZT12M09

西京医院学科助推计划 XJZT13Z01

西京医院学科助推计划 XJZT14Z04

详细信息
    作者简介:

    吴恩昊,男,1990年生,硕士,研究方向为普通外科的基础与临床研究,Email:waikeyisheng1224@163.com

    通讯作者:

    陶开山,男,1966年生,博士,教授,主任医师,研究方向为普通外科与器官移植,Email:taokaishan0686@163.com

  • 中图分类号: R617, R554+.8

Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation

More Information
  • 摘要:   目的  探讨异种肝移植术后导致受体凝血功能障碍的组织因子(TF)激活机制。  方法  实施3例α-1, 3-半乳糖基转移酶基因敲除(GTKO)小型猪-藏酋猴异种脾窝异位辅助性肝移植术。观察受体术后凝血功能变化情况。采用逆转录聚合酶链反应(RT-PCR)及免疫组织化学染色检测移植术前及术后不同时间点受体原肝和移植肝组织的猴TF及猪TF信使核糖核酸(mRNA)和蛋白的表达情况。检测正常对照猴、移植术前受体猴及移植术后2 h受体猴的外周血单核细胞(PBMC)的复钙时间以评价受体凝血状态。  结果  3例受体在术后均出现了不同程度的凝血功能障碍,表现为纤维蛋白原水平降低、血小板计数减少。猴TF蛋白在术后受体原肝中呈阳性表达,在术前及术后的移植肝中呈阴性表达;而猪TF蛋白在原肝和移植肝中始终为阴性表达。术后2 h,猴TF mRNA在原肝中较术前上调(2.10±0.24)倍,而猪TF在移植肝中较术前上调(1.42±0.15)倍,两者比较差异有统计学意义( P=0.014)。与正常对照猴PBMC和移植术前受体猴PBMC比较,术后2 h受体猴PBMC复钙时间明显缩短,差异均有统计学意义(均为 P < 0.001)。  结论  在异种肝移植术后凝血功能障碍发生时,受体原肝TF激活程度显著高于移植肝TF。受体原肝TF激活是导致异种肝移植术后凝血功能障碍的主要原因。

     

  • 图  1  异种肝移植术后受体凝血功能变化

    Figure  1.  Changes of coagulation function of recipients after liver xenotransplantation

    图  2  猴TF蛋白在原肝和移植肝中的表达情况(SP,×200)

    TF阳性细胞表现为细胞质内出现棕黄色颗粒

    Figure  2.  Expression of monkey TF protein in primary liver tissue and transplanted liver tissue

    图  3  猪TF蛋白在原肝和移植肝中的表达情况(SP,×200)

    TF阳性细胞表现为细胞质内出现棕黄色颗粒

    Figure  3.  Expression of pig TF protein in primary liver tissue and transplanted liver tissue

    图  4  原肝及移植肝组织中TF mRNA表达情况

    与术前比较,a P < 0.05

    Figure  4.  Expression of TF mRNA in primary liver tissue and transplanted liver tissue

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出版历程
  • 收稿日期:  2018-01-15
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2018-05-15

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