Release of danger signals during ischemic storage of the liver: a potential marker of organ damage?

Release of danger signals during ischemic storage of the liver: a potential marker of organ damage?
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DOI:
10.1155/2010/436145
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发表时间:
2010
影响因子:
4.6
通讯作者:
Dahmen U
Dahmen U
中科院分区:
医学3区
文献类型:
--
作者:
Liu A;Jin H;Dirsch O;Deng M;Huang H;Bröcker-Preuss M;Dahmen U

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移植肝在移植前由于缺血和操作等原因,不可避免地会受到损伤。危险信号如高迁移率族蛋白-1(HMGB1)和巨噬细胞移动抑制因子(MIF)在免疫反应中起着关键作用。我们研究了在冷/热缺血和额外的操作诱导的机械损伤期间,它们释放到流出物中的动力学。此外,我们还评估了HMGB1/MIF的释放与缺血/机械损伤的关系。肝脏流出物中的肝酶和蛋白质随缺血时间的延长而增加。HMGB1/MIF释放与肝细胞损伤程度相关。随着缺血时间的延长和损伤程度的增加,HMGB1从胞核转移到胞浆,表现为胞核较弱,胞浆染色较强。更早的HMGB1移位到细胞质和更早的危险信号释放到流出物中表明了机械性损伤对肝脏损伤的加强。我们的结果提示,HMGB1和MIF的测定反映了缺血损伤的程度。此外,HMGB1和MIF在检测外科手术过程中对器官移植物造成的额外机械损伤方面比肝酶更敏感。
Liver grafts suffer from unavoidable injury due to ischemia and manipulation before implantation. Danger signals such as high-mobility group box -1(HMGB1) and macrophage migration inhibitory factor (MIF) play a pivotal role in the immune response. We characterized the kinetics of their release into the effluent during cold/warm ischemia and additional manipulation-induced mechanical damage. Furthermore, we evaluated the relationship between HMGB1/MIF release and ischemic/mechanical damage. Liver enzymes and protein in the effluent increased with increasing ischemia time. HMGB1/MIF- release correlated with the extent of hepatocellular injury. With increasing ischemia time and damage, HMGB1 was translocated from the nucleus to the cytoplasma as indicated by weak nuclear and strong cytoplasmic staining. Enhancement of liver injury by mechanical damage was indicated by an earlier HMGB1 translocation into the cytoplasm and earlier release of danger signals into the effluent. Our results suggest that determination of HMGB1 and MIF reflects the extent of ischemic injury. Furthermore, HMGB1and MIF are more sensitive than liver enzymes to detect the additional mechanical damage inflicted on the organ graft during surgical manipulation.
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