CAJ | 학술논문

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(~(60)Co 8.5 Gy)和减低剂量TBI组(~(60)Co 5.0 Gy).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.
목적 탐토재조혈간세포이식전청수급비청수성전신조사(TBI)예처리대소서혈관내피적영향.방법 장6～8주령자성Balb/c소서수궤분위정상대조조(정상소서)、치사제량TBI조(~(60)Co 8.5 Gy)화감저제량TBI조(~(60)Co 5.0 Gy).TBI후정기관찰소서적생존상태,계수외주혈백세포;채용류식세포술검측외주혈중내피세포화내피조세포적변화;통과병리절편급투사전경관찰소서소장급간장적조직결구화혈관내피적초미결구.결과 치사제량TBI조소서외주혈백세포감소,동시내피세포급내피조세포증가,여정상소서상비,차이유통계학의의(P<0.05).감저제량TBI조소서외주혈백세포선강후승,내피세포여내피조세포동양야출현증가,여정상소서상비,차이유통계학의의(P<0.05);여치사제량TBI조비교,기외주혈내피세포화내피조세포증가폭도명현강저(P<0.05).량개TBI조소서적병리절편균가견간장실질세포수종급소장염증세포침윤,간장적초미결구가견혈관내피완정성수손,치사제량TBI조수손경위현저.결론 청수급비청수성제량TBI예처리균가인기소서혈관내피조기손상,기손상정도여제량상관,차외주혈중내피세포적변화가이반영혈관내피손상적정도.
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 ~(60)Co 8.5 Gy in a single dose given at a rate of 0.53 Gy/min); reduced irradiation group (exposed to ~(60)Co 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 (0.8×10~9/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 dayS) 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 endothelium damage in the liver and small intestine were milder compared to lethal irradiation group. Conclusion Vascular endothelial injury occurs in the mice given total body irradiation, and the degree of injury correlates with the dose of irradiation.