Evaluation of the effects of preconditioning regimens on hepatic veno-occlusive disease in mice after hematopoietic stem cell transplantation
Evaluation of the effects of preconditioning regimens on hepatic veno-occlusive disease in mice after hematopoietic stem cell transplantation
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预处理方案对造血干细胞移植后小鼠肝静脉闭塞性疾病的影响评价
DOI：
10.1016/j.yexmp.2014.12.008
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发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Zeng, Lingyu
中科院分区：
文献类型：
--
作者：
Qiao, Jianlin;Fu, Jinyu;Zeng, Lingyu
造血干细胞移植(HSCT)前的预适应方案，如全身照射(TBI)或白消安/环磷酰胺(BU/CY)，与肝静脉闭塞症(HVOD)相关。然而，这些方案治疗肝静脉闭塞症的机制尚不清楚。本研究的目的是评价TBI或BU/CY对小鼠HSCT后HVOD的影响。小鼠接受TBI或BU/CY，然后进行HSCT。观察肝脏病理和功能变化，并进行血小板聚集试验。两种方案均可损伤肝窦内皮细胞，导致肝窦正常结构完整性丧失、肝功能异常、纤维蛋白沉积、炎性细胞浸润和血小板聚集。两种方案对肝功能的影响无明显差异。肝脏脂滴增多。BU/CY组线粒体肿胀，HVOD发生率较高。综上所述，TBI和BU/CY均可引起肝窦内皮细胞的损伤，并可导致HVOD的发生，其中BU/CY的发生率较高。同时，还观察到炎症和血小板活化，提示靶向它们在预防HVOD中可能是有益的。(C)2014 Elsevier Inc.保留所有权利。
Pre-conditioning regimens before hematopoietic stem cell transplantation (HSCT), such as total body irradiation (TBI) or busulfan/cyclophosphamide (BU/CY), are associated with hepatic veno-occlusive disease (HVOD). However, the mechanism of these regimens on hepatic veno-occlusive disease remains unclear. The aim of this study is to evaluate the effect of TBI or BU/CY on HVOD in mice after HSCT. Mice received TBI or BU/CY followed by HSCT. Analysis of liver pathology and function, and platelet aggregation were performed. Both these regimens caused damage to liver sinusoid endothelial cells, leading to loss of normal structural integrity of liver sinusoid, abnormal liver function, fibrin deposition, inflammatory cells infiltration and platelet aggregation. No differences of liver function in these regimens were observed. Increased hepatic lipid droplets. mitochondrial swelling and higher incidence of HVOD were observed in BU/CY. In conclusion, both TBI and BU/CY caused damage to liver sinusoid endothelial cells and occurrence of HVOD with higher incidence for BU/CY. Meanwhile, inflammation and platelet activation was also observed, suggesting targeting them maybe beneficial in the prophylaxis of HVOD. (C) 2014 Elsevier Inc. All rights reserved.