骨髓移植后肝静脉闭塞病模型的鉴定及机制探讨  

Characterization of a reproducible mouse model of hepatic veno-occlusive disease

作　　者：孙海英[1] 徐开林[1] 安立才[1] 齐昆明[1] 潘彬[1] 房婷[1] 化静[1] 刘迷迷[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221002

出　　处：《中华器官移植杂志》2013年第1期42-46,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金（81070446）;江苏省科技创新人才项目（BK2007504）

摘　　要：目的建立异基因骨髓移植后肝静脉闭塞病（HVOD）模型并探索其发生机制。方法将Balb／c小鼠随机分为3组，即生理盐水对照组（NS组）、单纯照射组和单纯骨髓移植组。于移植后第0、5、10、15和20天检测各组小鼠肝重、外周血胆红素总量（TBi1）以及外周血肿瘤坏死因子a（TNF-a）、白细胞介素6（IL-6）和单核细胞趋化因子-1（MCP-1）浓度的变化，小鼠肝脏组织病理学改变。结果小鼠肝重和TBi1均于骨髓移植后第5天开始升高，第15天达到高峰。骨髓移植第5、10天小鼠肝脏以充血、水肿变化为主，肝组织存在炎症细胞浸润；第15、20天小鼠肝脏充血、水肿及坏死减轻，以肝脏纤维化为主要表现，炎症浸润明显。单纯照射组小鼠照射后10d内全部死亡，肝脏充血、水肿严重。与NS组小鼠相比较，单纯骨髓移植组小鼠TNF-a、IL-6和MCP-1浓度明显升高。结论成功建立异基因骨髓移植后肝静脉闭塞病模型。肝静脉闭塞病的机制与全身照射后造成的肝脏内皮损伤、炎症细胞浸润及移植后细胞因子的变化密切相关。Objective To establish a reproducible mouse model of hepatic veno-occlusive disease （HVOD） after allogeneic bone marrow transplantation （aallo-ABMT） and explore its pathogenesis. Methods Balb/c mice were randomly divided into three groups： （1） normal saline （NS） control group; （2） total body irradiation （TBI） group; （3） allogeneic bone marrow transplantation （allo-BMT） group. Liver weight, total bilirubin （ TBil ）, tumor necrosis factor a （TNF-a）, interleukin 6 （IL-6） and monocyte chemotactic protein 1 （MCP-1） were detected on the day 0, 5, 10, 15 and 20 after transplantation. Hepatic vein and sinusoid congestion, infiltration of inflammatory cells, and damage to hepatic cells and vascular endothelial cells were observed under the light microscopy after HE staining. Fibrosis of hepatic sinusoids and venule was observed under the light microscopy after Masson staining. Results Liver weight and TBil levels were elevated at 5th day and reached the peak at 15th day after all-ABMT. The changes of hepatic congestion and edema were obviously observed and there was infiltration of inflammatory cells at 5th and 10th day after alloABMT. At 15th and 20th day, hepatic congestion, edema and necrosis were reduced and liver damage was mainly presented with liver fibrosis and inflammatory infiltration. All mice died within 10 days after TB1, and hepatic congestion and edema were aggravated. As compared with NS control group, TNF-a, IL-6 and MCP-1 concentrations were significantly increased after all-ABMT. Conclusion A reproducible mouse model of hepatic veno-occlusive disease after all-ABMT was successfully established, and the pathogenesis was closely related to endothelial damage caused hy total body irradiation, inflammatory cell infiltration and increased concentrations of cytokines.

关 键 词：造血干细胞移植 内皮细胞 肝静脉闭塞性疾病 细胞因子类 

分 类 号：R457.7[医药卫生—治疗学]