Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liver
Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liver
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DOI：
10.1002/hep.20157
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发表时间：
2004-04-01
期刊：
影响因子：
13.5
通讯作者：
Bilodeau, M
中科院分区：
文献类型：
--
作者：
Huet, PM;Nagaoka, MR;Bilodeau, M
肝脏的冷缺血-温再灌注（CI-WR）损伤的特点是肝窦内皮细胞（SEC）的显着改变，而肝细胞似乎相对未受影响。然而，细胞死亡的时间过程和机制仍然存在争议：早期现象还是晚期现象，坏死还是凋亡？我们描述了在离体灌注大鼠肝脏模型中使用威斯康星大学 (UW) 溶液进行不同时期的 CI 后以及不同时期的 WR 后细胞死亡的发生和性质。 24 小时和 42 小时 CI（分别为活肝脏和非活肝脏）后，观察到类似的肝细胞死亡模式：WR 后（10 分钟）早期出现 SEC 坏死，并保持稳定长达 120 分钟。 VIR 30 分钟后，细胞凋亡随着 WR 长度的增加而逐渐增加。根据形态学标准，凋亡细胞主要是肝板内或肝窦腔内挤出的肝细胞。此外，仅在 42 小时 Cl 后，在血窦充血区域才发现大簇坏死肝细胞。在这些相同的肝脏中，通过多指标稀释技术评估的肝脏微循环显示，细胞外基质消失并出现无流动区域。总之，CI-WR 后大鼠肝脏中出现不同的细胞死亡时程和机制，早期 SEC 坏死，随后肝细胞凋亡延迟。这些过程在移植失败的机制中似乎并不重要，因为它们在非致死和致死条件下都是相似的。但细胞外基质的损失却并非如此，这种情况仅在致死条件下发生且与肝细胞坏死有关。
Cold ischemia-warm reperfusion (CI-WR) injury of the liver is characterized by marked alterations of sinusoidal endothelial cells (SECs), whereas hepatocytes appear to be relatively unscathed. However, the time course and mechanism of cell death remain controversial: early versus late phenomenon, necrosis versus apoptosis? We describe the occurrence and nature of cell death after different periods of CI with University of Wisconsin (UW) solution and after different periods of WR in the isolated perfused rat liver model. After 24- and 42-hour CI (viable and nonviable livers, respectively), similar patterns of liver cell death were seen: SEC necrosis appeared early after WR (10 minutes) and remained stable for up to 120 minutes. After 30 minutes of VIR, apoptosis increased progressively with WR length. Based on morphological criteria, apoptotic cells were mainly hepatocytes within liver plates or extruded in the sinusoidal lumen. In addition, only after 42-hour Cl were large clusters of necrotic hepatocytes found in areas of congested sinusoids. In these same livers, the hepatic microcirculation, evaluated by means of the multiple-indicator dilution technique, revealed extracellular matrix disappearance with no-flow areas. In conclusion, different time courses and mechanisms of cell death occur in rat livers after CI-WR, with early SEC necrosis followed by delayed hepatocyte apoptosis. These processes do not appear to be of major importance in the mechanism of graft failure because they are similar under both nonlethal and lethal conditions; this is not the case for the loss of the extracellular matrix found only under lethal conditions and associated with hepatocyte necrosis.