Reduced expression of the melanocortin-1 receptor in human liver during brain death
Reduced expression of the melanocortin-1 receptor in human liver during brain death
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DOI：
10.1159/000094513
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发表时间：
2006-01-01
影响因子：
2.4
通讯作者：
Catania, Anna
中科院分区：
文献类型：
--
作者：
Gatti, Stefano;Colombo, Gualtiero;Catania, Anna
目的：有证据表明脑死亡对周围器官有损害作用。对器官捐赠者的临床和实验研究表明，在脑死亡期间收集的肝脏和肾脏组织样本中存在明显的炎症。炎症反应的特征是细胞因子的释放和炎性细胞浸润。由于黑皮质素及其受体是炎症的重要调节剂，我们假设在脑死亡过程中黑皮质素受体的调节可能有助于增强炎症。研究方法：使用实时聚合酶链反应（PCR）分析，我们确定了黑皮质素受体的表达在肝活检获得脑死亡器官供体冷缺血前和正常肝组织切除良性病灶的肝脏。还分析了组织活检中细胞间粘附分子-1（ICAM-1）的表达，ICAM-1在炎症细胞迁移中具有重要作用。结果如下：黑素皮质素-1受体（MC 1 R）mRNA的表达显着减少，从braindead器官捐赠者的肝脏样本相比，在切除肝脏良性病灶的肝组织收集。相反，在脑死亡器官捐赠者的肝脏中，粘附分子ICAM-1的表达显著增加。结论：基于MC 1 R的内源性抗炎通路的破坏可能导致脑死亡期间的组织损伤。版权所有（c）2006 S. Karger AG，巴塞尔。
Objective:There is evidence that brain death has detrimental effects on peripheral organs. Clinical and experimental studies on organ donors showed marked inflammation in tissue samples of livers and kidneys collected during brain death. The inflammatory reaction is characterized by release of cytokines and inflammatory cell infiltration. Because melanocortins and their receptors are significant modulators of inflammation, we hypothesized that clownregulation of melanocortin receptors during brain death could contribute to enhance inflammation. Methods: Using real-time polymerase chain reaction (PCR) analysis, we determined expression of melanocortin receptors in liver biopsies obtained from brain-dead organ donors before cold ischemia and in normal liver tissue during resection of benign focal lesions of the liver. Tissue biopsies were also analyzed for expression of intercellular adhesion molecule-1 (ICAM-1), which has a central function in inflammatory cell migration. Results: Expression of melanocortin-1 receptor (MC1R) mRNA was markedly reduced in liver samples obtained from braindead organ donors compared to hepatic tissue collected during resection of benign focal lesions of the liver. Conversely, expression of the adhesion molecule ICAM-1 was significantly increased in livers of brain-dead organ donors. Conclusions: Disruption of the endogenous anti-inflammatory circuit based on MC1R could contribute to tissue damage during brain death. Copyright (c) 2006 S. Karger AG, Basel.