CAJ | 학술논문

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(TBil)以及外周血肿瘤坏死因子α(TNF-α)、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TBil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10 d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-α、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.
목적 건립이기인골수이식후간정맥폐새병(HVOD)모형병탐색기발생궤제.방법 장Balb/c소서수궤분위3조,즉생리염수대조조(NS조)、단순조사조화단순골수이식조.우이식후제0、5、10、15화20천검측각조소서간중、외주혈담홍소총량(TBil)이급외주혈종류배사인자α(TNF-α)、백세포개소6(IL-6)화단핵세포추화인자-1(MCP-1)농도적변화,소서간장조직병이학개변.결과 소서간중화TBil균우골수이식후제5천개시승고,제15천체도고봉.골수이식제5、10천소서간장이충혈、수종변화위주,간조직존재염증세포침윤；제15、20천소서간장충혈、수종급배사감경,이간장섬유화위주요표현,염증침윤명현.단순조사조소서조사후10 d내전부사망,간장충혈、수종엄중.여NS조소서상비교,단순골수이식조소서TNF-α、IL-6화MCP-1농도명현승고.결론 성공건립이기인골수이식후간정맥폐새병모형.간정맥폐새병적궤제여전신조사후조성적간장내피손상、염증세포침윤급이식후세포인자적변화밀절상관.
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 α (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 inflanmatory 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 TBI,and hepatic congestion and edema were aggravated.As compared with NS control group,TNF-α,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 by total body irradiation,inflammatory cell infiltration and increased concentrations of cytokines.