Qi K, Li H, An L, Song G, Pan B, Chen W, Wang Z, Zhang C, Fang T, Hua J, Liu M, Wu Q, Cao J, Li Z, Zeng L, Xu K
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, Peoples Republic of China.
Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, Peoples Republic of China.
Transplant Proc. 2014 Jun;46(5):1523-30. doi: 10.1016/j.transproceed.2014.02.025.
Hepatic veno-occlusive disease (HVOD) is a common severe complication after transplantation which is closely related to liver sinusoidal endothelial cell (LSEC) injury. Although platelet activation might play a key role in the progress of HVOD, the relationship between the P-selectin and HVOD is still unclear. In this study, the P-selectin, liver functions, and observed damage of LSEC after transplantation were detected. The P-selectin, alanine aminotransferase (ALT) and bilirubin were first detected in the patients. The ALT of patients reached the first peak of 144 ± 45.04 U/L, on day 7 after busulfan + cyclophosphamide (BU/CY) pretreatment, and reached the second peak of 220.5 ± 40.58 U/L on day 7 after transplantation. Similarly, the concentration of bilirubin increased BU/CY pretreatment and reached peak on day 15 after transplantation at 38.8 ± 5.99 μmol/L. However, the level of P-selectin was significantly higher than normal levels for a long time and peaked on day 3 after BU/CY pretreatment and on day 12 after transplantation (P < .05). Then the P-selectin, liver function, liver index, hepatocytes, and LSEC were observed using a transplantation model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient. The P-selectin, liver index, and liver function of total body irradiation (TBI) mice and bone marrow transplantation (BMT) mice were significantly increased, but the increase of TBI mice were more significant. On day 5, the ratio of TBI mice peripheral blood platelets which expressed P-selectin was higher and reached an earlier peak at 15.6 ± 2.63%, whereas that of BMT mice was 6.59 ± 1.17%, and peaked on day 15 at 8.36 ± 1.55% (P < .05). Moreover, the ALT and bilirubin levels of TBI mice were higher and reached earlier peaks on day 5 at 58.65 ± 1.43 U/L and 27.14 ± 1.32 μmol/L, respectively, whereas those of BMT mice peaked on day 5 at 50.22 ± 2.02 U/L and day 30 at 39.57 ± 1.55 μmol/L, respectively (P < .05). The LSEC damage and hepatocyte edema in BMT mice were most serious at day 15, and at day 30 injuries did not allow recovery. The liver score of TBI mice peaked on day 5, whereas that of BMT mice peaked on day 15. Moreover, the degree of damage and platelet activation positively correlated. This study implied that P-selectin could be used as a predictor of HVOD.
肝静脉闭塞病（HVOD）是移植术后常见的严重并发症，与肝血窦内皮细胞（LSEC）损伤密切相关。尽管血小板活化可能在HVOD进展中起关键作用，但P-选择素与HVOD之间的关系仍不清楚。本研究检测了移植后P-选择素、肝功能及LSEC的损伤情况。首先检测了患者的P-选择素、丙氨酸转氨酶（ALT）和胆红素。患者的ALT在白消安+环磷酰胺（BU/CY）预处理后第7天达到第一个峰值144±45.04 U/L，并在移植后第7天达到第二个峰值220.5±40.58 U/L。同样，胆红素浓度在BU/CY预处理后升高，并在移植后第15天达到峰值，为38.8±5.99 μmol/L。然而，P-选择素水平在很长一段时间内显著高于正常水平，并在BU/CY预处理后第3天和移植后第12天达到峰值（P<0.05）。然后，利用C57BL/6（H-2(b)）供体至BALB/c（H-2(d)）受体的移植模型观察P-选择素、肝功能、肝脏指数、肝细胞和LSEC。全身照射（TBI）小鼠和骨髓移植（BMT）小鼠的P-选择素、肝脏指数和肝功能显著升高，但TBI小鼠的升高更显著。在第5天，TBI小鼠外周血中表达P-选择素的血小板比例更高，在第15.6±2.63%时更早达到峰值，而BMT小鼠为6.59±1.17%，并在第15天达到峰值，为8.36±1.55%（P<0.05）。此外，TBI小鼠的ALT和胆红素水平更高，并分别在第5天达到更早的峰值，分别为58.65±1.43 U/L和27.14±1.32 μmol/L，而BMT小鼠分别在第5天达到峰值，为50.22±2.02 U/L，在第30天达到峰值，为39.57±1.55 μmol/L（P<0.05）。BMT小鼠的LSEC损伤和肝细胞水肿在第15天最严重，到第30天损伤无法恢复。TBI小鼠的肝脏评分在第5天达到峰值，而BMT小鼠在第15天达到峰值。此外，损伤程度与血小板活化呈正相关。本研究表明，P-选择素可作为HVOD的预测指标。
