Department of Anesthesiology and Reanimation, Ege University School of Medicine, Izmir, Turkey.
Clin Transplant. 2010 Nov-Dec;24(6):848-54. doi: 10.1111/j.1399-0012.2009.01177.x.
Hepatocellular damage takes place as a result of ischemia and reperfusion during liver transplantation (LT). To discriminate the type of cell death and quantitate its severity may provide new insights into the mechanisms of hepatocellular damage. Therefore, we investigated the type of cell death by ELISA-based assays in patient sera. Apoptosis was specifically assessed by measuring a novel soluble biomarker, the caspase-cleaved cytokeratin 18, while total cell death (apoptosis and necrosis) by cytokeratin 18 released from dead (necrotic and apoptotic) cells. Twenty-seven live (LDLT) and 14 deceased (DDLT) donor liver transplantations were analyzed before the operation, at the anhepatic stage, first, sixth and 24th hour after the reperfusion. Both apoptosis and total cell death have successfully been demonstrated although they have not been confirmed by the liver biopsy that is impossible to perform in this setting. Apoptosis was not induced in LDLT. Total cell death (primarily necrosis) only transiently appeared the first hour after the reperfusion in LDLT, while it sharply increased the first hour after the reperfusion and maintained its level in DDLT. Soluble cytokeratin 18 biomarkers seem to be useful to discriminate and quantitate the type of cell death during early ischemia and reperfusion periods of LT.
在肝移植（LT）过程中，肝脏会因缺血再灌注而发生肝细胞损伤。区分细胞死亡的类型并定量其严重程度，可能为深入了解肝细胞损伤的机制提供新的见解。因此，我们通过 ELISA 检测患者血清中的细胞死亡类型。通过测量新型可溶性生物标志物半胱氨酸蛋白酶切割细胞角蛋白 18 来特异性评估细胞凋亡，而通过从死亡（坏死和凋亡）细胞释放的细胞角蛋白 18 来定量总细胞死亡（凋亡和坏死）。分析了 27 例活体（LDLT）和 14 例已故（DDLT）供体肝移植患者在手术前、无肝期、再灌注后第 1、6 和 24 小时的血清样本。虽然在无法进行肝活检的情况下无法进行验证，但我们成功地证明了凋亡和总细胞死亡。LDLT 中未诱导细胞凋亡。LDLT 中，再灌注后第 1 小时仅短暂出现总细胞死亡（主要是坏死），而 DDLT 中，再灌注后第 1 小时急剧增加，并维持其水平。可溶性细胞角蛋白 18 生物标志物似乎可用于区分和定量 LT 早期缺血再灌注期间的细胞死亡类型。
