造血干细胞移植前清髓及非清髓性照射预处理对小鼠血管内皮的影响  

Effects of irradiation pretreatment on vascular endothelial cells in mice during hematopoietic stem cell transplantation

作　　者：孙海英[1] 闫志凌[1] 许世娟[1] 丁爽[1] 贾路[1] 陈翀[1] 曹江[1] 曾令宇[1] 

机构地区：[1]徐州医学院附属医院血液科,江苏221002

出　　处：《中华器官移植杂志》2009年第11期686-689,共4页Chinese Journal of Organ Transplantation

基　　金：江苏省自然科学基金创新人才项目（BK2007504）

摘　　要：目的探讨在造血干细胞移植前清髓及非清髓性全身照射（TBI）预处理对小鼠血管内皮的影响。方法将6～8周龄雌性Balb／c小鼠随机分为正常对照组（正常小鼠）、致死剂量TBI组（^66Co8．5Gy）和减低剂量TBI组（^60Co5．0Gy）。TBI后定期观察小鼠的生存状态，计数外周血白细胞；采用流式细胞术检测外周血中内皮细胞和内皮祖细胞的变化；通过病理切片及透射电镜观察小鼠小肠及肝脏的组织结构和血管内皮的超微结构。结果致死剂量TBI组小鼠外周血白细胞减少，同时内皮细胞及内皮祖细胞增加，与正常小鼠相比，差异有统计学意义（P〈0．05）。减低剂量TBI组小鼠外周血白细胞先降后升，内皮细胞与内皮祖细胞同样也出现增加，与正常小鼠相比，差异有统计学意义（P〈0．05）；与致死剂量TBI组比较，其外周血内皮细胞和内皮祖细胞增加幅度明显降低（P〈0．05）。两个TBI组小鼠的病理切片均可见肝脏实质细胞水肿及小肠炎症细胞浸润，肝脏的超微结构可见血管内皮完整性受损，致死剂量TBI组受损更为显著。结论清髓及非清髓性剂量TBI预处理均可引起小鼠血管内皮早期损伤，其损伤程度与剂量相关，且外周血中内皮细胞的变化可以反映血管内皮损伤的程度。Objective To explore the endothelial injury in mice with different doses of total body irradiation （TBI） for pre-treatment in hematopoietic stem cell transplantation （HSCT）. Methods Six-eight-week-old female Balb/c mice were divided into three groups randomly： control group; lethal irradiation group （exposed to ^60Co 8. 5 Gy in a single dose given at a rate of 0. 53 Gy/min） ; reduced irradiation group （exposed to ^60Co 5.0 Gy in a single dose given at a rate of 0. 53 Gy/min）. The general state of the mice were observed, harvested peripheral white blood cells were counted and changes in endothelial cells （ECs） and endothelial progenitor cells （EPCs） were examined by flow cytometry regularly. The morphologic changes of endothelia were observed under a light microscope and ultrastructure of tissue by a transmission electron microscope （TEM）. Results In lethal irradiation group, circulating WBCs were less than 0. 5 × 10^9/L at the day 3, while circulating ECs increased and had a peak at the day 5, about 6. 4 folds as that of control （P〈0.05） and circulating EPCs reached the peak at the day 5, about 24.9 folds as that of control （P〈0.05）. Extensive parenchyma cells edema and few lymphocytes infiltration in the portal area of liver was found on the 5th day, but the ultrastructure of hepatic sinusoid ECs showed that nuclear fragmentation, and nuclear chromatin gathered toward the margin and the endothelium integrity was destroyed. In reduced irradiation group, circulating WBCs started to decrease from the day 3 and to the lowest （（1.8 ×10^9/L） at the day 7, and then recovered to the normal level gradually. Circulating ECs, compared to lethal irradiation group, were increased and reached the peak latterly （increase： day 5 vs day 3, peak： day 7 vs day5） and the amplitude was lower （P〈0. 05）. Circulating EPCs were elevated earlier （day 1）, but the amplitude was lower than the lethal irradiation group （P〈0. 05）. The pathological changes and endotheliu

关 键 词：移植预处理 全身照射 内皮 血管 损伤 

分 类 号：R686[医药卫生—骨科学]