Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver
Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver
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DOI：
10.1016/s0016-5085(00)70427-6
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发表时间：
2000-01-01
期刊：
影响因子：
29.4
通讯作者：
Clavien, PA
中科院分区：
文献类型：
--
作者：
Sindram, D;Porte, RJ;Clavien, PA
背景与目的：正弦内皮细胞（SEC）凋亡是肝移植再灌注损伤的核心特征。移植后发生血小板隔离，可能产生有害影响。我们测试了血小板介导 SEC 细胞凋亡的假设。方法：采用威斯康星大学溶液冷保存24小时后对离体大鼠肝脏灌注模型进行肝脏灌注。灌注液含有分离的同基因红细胞和纯化的血小板。使用选择素粘附分子的天然配体唾液酸路易斯-X寡糖(sLe(x))测试抑制血小板粘附对SEC细胞凋亡的影响。通过已建立的损伤标志物评估再灌注损伤。通过TUNEL和电子显微镜测定细胞凋亡。结果：再灌注后，三分之一的循环血小板迅速被隔离在肝脏中。这与移植物损伤增加有关。单个血小板粘附在血窦内壁上，没有微循环损害的形态学或动态证据。 TUNEL 染色显示再灌注 1 小时时凋亡 SEC 的数量增加了 6 倍。再灌注 3 小时内未检测到肝细胞死亡或坏死证据。添加 sLe(x) 可抑制粘附并显着减少 SEC 细胞凋亡。结论：移植肝再灌注时血小板可引起SEC凋亡，预防粘连具有保护作用。
Background & Aims: Sinusoidal endothelial cell (SEC) apoptosis is a central feature of reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation with possible deleterious effects. We tested the hypothesis that platelets mediate SEC apoptosis. Methods: Livers were perfused after 24 hours of cold preservation in University of Wisconsin solution in an isolated perfused rat liver model. The perfusate contained isolated syngeneic red blood cells and purified platelets. Effects of inhibiting platelet adhesion on SEC apoptosis was tested using sialyl Lewis-X oligosaccharide (sLe(x)), a natural ligand of selectin adhesion molecules. Reperfusion injury was assessed by established markers of injury. Apoptosis was determined by TUNEL and electron microscopy. Results: A third of the circulating platelets was rapidly sequestered in the liver after reperfusion. This was associated with increased graft injury. Single platelets were adherent to sinusoidal lining without morphological or dynamic evidence of impairment of microcirculation. TUNEL staining revealed a 6-fold increase in the number of apoptotic SECs at 1 hour of reperfusion. No hepatocyte death or evidence of necrosis was detected up to 3 hours of reperfusion. Addition of sLe(x) inhibited adhesion and significantly reduced SEC apoptosis. Conclusions: Platelets cause SEC apoptosis upon reperfusion of liver grafts, Prevention of adhesion is protective.