CAJ | 학술논문

目的研究联合内皮祖细胞(EPC)移植对小鼠骨髓移植预处理中肝脏内皮损伤的修复作用.方法将C57BL/6小鼠分为4组,每组10只.(1)正常对照组:小鼠不做任何处理,仅作为正常对照;(2)单纯照射组:单次给予全身照射(TBI)预处理,不进行骨髓移植;(3)单纯移植组:给予单纯照射组相同的TBI预处理,TBI后4 h内经小鼠尾静脉输注C57BL/6小鼠骨髓单个核细胞5×106/只;(4)联合移植组,小鼠的处理方式与单纯移植组相同,仅在骨髓移植的同时经尾静脉输注C57BL/6小鼠EPC 5×105/只.TBI后第2、4、7、14、21天,检测各组小鼠肝脏重量的变化情况,并于TBI后第4、7、14、21天对各组小鼠肝脏进行组织病理学检查.结果单纯照射组、单纯移植组和联合移植组小鼠肝脏重量均于TBI后第2天开始明显增加,于第14天达到高峰,峰值分别为正常对照组的(1.65±0.15)倍(P＜0.05)、(1.61±0.06)倍(P＜0.05)和(1.11±0.4(0)倍(P＜0.05);以后均呈下降趋势,第21天时单纯照射组和单纯移植组肝脏重量仍明显高于正常对照组(P＜0.05),但联合移植组小鼠肝脏重量已完全恢复正常.组织病理学检查显示,单纯照射组小鼠肝窦内皮损伤明显,肝细胞水肿及严重的炎症细胞浸润,第7天时肝细胞水肿、坏死较前明显加重,几乎无存活的肝血窦内皮细胞;第14天时单纯移植组小鼠肝窦内皮损伤较前有所减轻,但到第21天时仍未恢复正常;联合移植组小鼠第7天时肝窦内皮及肝细胞水肿、坏死程度均较轻,到第14天时已基本恢复正常.结论造血干细胞移植前的预处理会造成受者肝脏内皮损伤,且此损伤持续存在;移植时联合输注EPC能修复肝窦内皮的损伤.
목적 연구연합내피조세포(EPC)이식대소서골수이식예처리중간장내피손상적수복작용.방법 장C57BL/6소서분위4조,매조10지.(1)정상대조조:소서불주임하처리,부작위정상대조;(2)단순조사조:단차급여전신조사(TBI)예처리,불진행골수이식;(3)단순이식조:급여단순조사조상동적TBI예처리,TBI후4 h내경소서미정맥수주C57BL/6소서골수단개핵세포5×106/지;(4)연합이식조,소서적처리방식여단순이식조상동,부재골수이식적동시경미정맥수주C57BL/6소서EPC 5×105/지.TBI후제2、4、7、14、21천,검측각조소서간장중량적변화정황,병우TBI후제4、7、14、21천대각조소서간장진행조직병이학검사.결과 단순조사조、단순이식조화연합이식조소서간장중량균우TBI후제2천개시명현증가,우제14천체도고봉,봉치분별위정상대조조적(1.65±0.15)배(P＜0.05)、(1.61±0.06)배(P＜0.05)화(1.11±0.4(0)배(P＜0.05);이후균정하강추세,제21천시단순조사조화단순이식조간장중량잉명현고우정상대조조(P＜0.05),단연합이식조소서간장중량이완전회복정상.조직병이학검사현시,단순조사조소서간두내피손상명현,간세포수종급엄중적염증세포침윤,제7천시간세포수종、배사교전명현가중,궤호무존활적간혈두내피세포;제14천시단순이식조소서간두내피손상교전유소감경,단도제21천시잉미회복정상;연합이식조소서제7천시간두내피급간세포수종、배사정도균교경,도제14천시이기본회복정상.결론 조혈간세포이식전적예처리회조성수자간장내피손상,차차손상지속존재;이식시연합수주EPC능수복간두내피적손상.
Objective To study the repair function of united endothelial progenitor cells (EPC)transplantation on injured liver endothelium by bone marrow transplantation (BMT) conditioning.Methods C57BL/6 mice were divided into four groups randomly: normal control group, without any treatment; irradiation alone group, administered a total body irradiation(TBI) pretreatment, without BMT; (3) BMT alone group: C57BL/6 mice were infused with bone marrow mononuclearcells (MNC) 5 × 106/only through caudal vein not more than 4 h after the same TBI pretreatment as the irradiation alone group; united transplantation group: receiving the same way as the BMT alone group, but C57BL/6 mice were infused with EPC 5 × 105/only at the same time. Two, 4, 7, 14, and 21 days after the TBI, the changes of the liver weight were observed regularly. The histopathological examination of liver was done at the 4th, 7th, 14th, and 21st day after the TBI. Results In irradiation alone group, BMT alone group and united transplantation group the liver weight began to increase significantly on the day 2 and peaked at 14th day after the TBI, and the peaks were respectively (1.65±0. 15) times (P＜0. 05), (1.61 ±0.06) times (P＜0.05), and (1.11 ±0.40)times (P＜0. 05) of those in normal control group. At the day 14, the liver weight in irradiation alone group, BMT alone group and united transplantation group began to decrease, and on the day 21 the liver weight in united transplantation group had been completely restored to normal level, however the liver weight in irradiation alone group and BMT alone group were still significantly heavier than that in normal control group (P＜0. 05). Liver histopathological examination revealed that there were obvious sinusoidal endothelial cells (SEC) injury, hepatocyte edema and severe inflammatory cell infiltration in irradiation alone group, and on the day 7 the hepatocyte edema and necrosis were significantly worse than before, and almost no alive SEC were found. On the day 14 the injury of SEC in BMT alone group was lighter than before, but on the day 21 the injury had not returned to normal. On the day 7 the injury of SEC, hepatocyte edema and necrosis were alleviated in united transplantation group as compared with irradiation alone group and BMT alone group, and on the day 14 the injury had returned to normal basically. Conclusion The transplantation conditioning could damage recipient liver endothelium and the injury would persist, and united EPC infusion could repair the injured SEC following BMT.