小鼠肝窦内皮细胞损伤在肝静脉闭塞病中的作用研究  

Effects of Liver Sinusoid Endothelial Cell Injury in Mouse Hepatic Veno-occlusive Disease

作　　者：房婷[1] 安立才[1] 刘迷迷[1] 化静[1] 徐开林[1,2] 曾令宇[1,2] 

机构地区：[1]徐州医学院附属医院血液科,江苏徐州221002 [2]徐州医学院移植免疫实验室,江苏徐州221002

出　　处：《中国实验血液学杂志》2012年第6期1457-1462,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号81070446)

摘　　要：本研究探讨野百合碱诱导的小鼠肝窦内皮细胞损伤在肝静脉闭塞病中的作用。将BALB/c小鼠随机分为2组,即生理盐水组(n=15)和野百合碱组(n=15),分别按10 ml/kg和200 mg/kg灌胃,连续3 d。灌胃后第3、4、6、8和10天检测各组小鼠肝功能(总胆红素、丙氨酸转氨酶、碱性磷酸酶)、肝脏指数及活化血小板比例;HE染色、Masson染色及免疫组织化学染色观察肝细胞及肝窦内皮细胞的损伤情况、肝脏纤维化程度等;电子显微镜观察肝窦内皮细胞损伤、炎细胞浸润及血小板聚集情况。结果显示,野百合碱组与生理盐水组相比在光学显微镜和电子显微镜下均可见肝窦内皮细胞损伤、大量血小板黏附和聚集、中央静脉和肝血窦纤维化;与生理盐水组相比,野百合碱组外周血活化血小板比例升高(P<0.05),肝脏指数升高(P<0.05),肝功能异常并有腹水形成。结论:野百合碱诱导的肝窦内皮细胞损伤是肝静脉闭塞病的始动因素,且该肝窦内皮细胞损伤可能具有自限性,但纤维化持续存在。This study was purposed to investigate the role of monocrotaline-inducing mouse liver sinusoid endothelial cell （SEC） injury in hepatic veno-occlusive disease. BALB/c mice were randomly divided into 2 groups：control group and monocrotaline group, mice were orally administrated with normal saline or monocrotaline with concentration of 200 mg/kg at days 0,1,2, respectively. At days 3,4,6,8 and 10 after oral administration with normal saline or monocrotaline, the liver function（ALT, TBIL, AKP ）and liver index were examined, and the percentage of activated platelets were detected by flow cytometry. The SEC, vascular endothelial cells and hepatic fibrosis were observed by staining with hematoxylin-eosin and Masson. Transmission electron microscopy was used to observe sinusoidal endothelial cell damage and platelet adhe- sion. The results showed that compared with control group, mice in monocrotaline group were characterized by severe damage of SEC, numbers of platelet aggregation and adhesion, central number and sinusoidal fibrosis. The percentage of activated platelets and liver index increased （P 〈 0.05 ）. The characterization of portal hypertension was presented later, such as dysfunction of liver and ascites. It is concluded that SEC injury induced by monocrotaline may be the first step of hepatic veno-occlusive disease,and this kind of SEC injury is self-limiting, but fibrosis is always observed.

关 键 词：肝窦内皮细胞 肝静脉闭塞病 野百合碱 造血干细胞移植 

分 类 号：R575[医药卫生—消化系统] R457.7[医药卫生—内科学]