内皮祖细胞抑制小鼠异基因骨髓移植后肝小静脉血栓形成的作用  

Inhibition of endothelial progenitor cells against hepatic vein thrombosis after allogeneic bone marrowtransplantation

作　　者：安立才[1] 孙海英[1] 徐开林[1] 齐昆明[1] 宋国梁[1] 潘彬[1] 曾令宇[1] 

机构地区：[1]徐州医学院附属医院血液科徐州医学院移植免疫实验室, 江苏省徐州市221002

出　　处：《中华器官移植杂志》2012年第10期629-633,共5页Chinese Journal of Organ Transplantation

基　　金：：国家自然科学基金（81070446）;新世纪优秀人才支持计划（NCET09-0166）

摘　　要：目的探讨内皮祖细胞（EPC）抑制异基因骨髓移植后肝小静脉血栓形成的作用。方法采用随机数字表法将Balb／c小鼠分为3组，单纯骨髓移植组的小鼠在全身照射后经尾静脉输注C57BL／6小鼠的骨髓单个核细胞5×10^5／只；联合EPC移植组则在单纯骨髓移植的基础上同时输注伤7BL／6小鼠的EPC5X10^5／只；正常对照组的小鼠不作任何处理。分别于移植后第0、5、10、15和20天时，计算各组小鼠的肝脏指数，光镜下观察肝小静脉血栓形成情况以及肝细胞及血管内皮损伤情况，电镜下观察肝小静脉、肝血窦内皮、肝细胞损伤及血小板黏附情况，检测外周血活化血小板的比例及肿瘤坏死因子a（TNF-c0浓度的变化。结果移植后第0、5、10、15和20天时，单纯骨髓移植和联合EPC移植组的活化血小板比例、肝脏指数和外周血TNF-a浓度均呈现上升趋势，至第15天时达到高峰，随后下降，但仍明显高于正常对照组（P〈0．05）；各时间点联合EPC移植组的上述指标均明显低于单纯骨髓移植组，差异均有统计学意义（P〈0．05）。与单纯骨髓移植组比较，联合EPC移植组的血小板黏附减少，肝小静脉血栓形成较少，肝细胞水肿和坏死程度均较轻，且肝脏损伤修复较快。绪论小鼠骨髓移植时联合输注EPC能显著抑制肝小静脉血栓形成，明显减轻肝脏损伤。Objective To explore inhibition of endothelial progenitor cells （EPCs） against hepatic vein thrombosis after allogeneic bone marrow transplantation （BMT）. Methods Balb/c mice were randomly divided into three groups： （1） BMT group [Balb/c mice were injected intravenously with 5 x 106 bone marrow cells after total body irradiation （TBD];（2） EPCs co-transfusion with bone marrow cells group; 5 x 105 EPCs were infused into recipient mice simultaneously; （3） Normal control group. Liver index was detected on the day 0, 5, 10, 15 and 20 after transplantation. Hepatic vein thrombosis, hepatic cells and vascular endothelial damage were observed under the light microscopy after H^E staining. The injury of liver cells, liver veins, hepatic sinusoidal endothelial cells （SECs） and platelet adhesion conditions were observed under a transmission electron microscope （TEM）. The proportion of activated platelets and TNF-a concentration in peripheral blood were detected by using flow cytometry. Results On the day 0, 5, 10, 15 and 20 after transplantation, the proportion of activated platelets, liver index and TNF-a concentrations in BMT group and EPCs co-transfusion group showed an upward trend, peaked on the 15th day, and then decreased. However, they were still significantly higher than those in normal control group （P〈0. 05）. The above parameters in EPCs co-transfusion group at each time point were significantly lower than those in BMT group （P〈 0. 05）. As compared with BMT group, platelet adhesion decreased, hepatic vein thromboses were reduced, hepatocyte swelling and necrosis were alleviated, and liver damage repaired rapidly in EPCs co-transfusion group. Conclusion EPCs co-transfusion with bone marrow cells could inhibit the hepatic veins thrombosis and ameliorate liver damage significantly.

关 键 词：内皮祖细胞 内皮 异基因骨髓移植 肝小静脉血栓 

分 类 号：R457.7[医药卫生—治疗学]