内皮损伤相关因子在小鼠肝小静脉闭塞病模型中的表达

随着中草药的广泛应用,近年我国因误服含吡咯烷类生物碱（PAs）的中草药致肝小静脉闭塞病（HVOD）的报道逐渐增多.目的：探讨内皮细胞损伤及其相关因子在HVOD发病中的作用.方法：分别以土三七灌胃30 d和野百合碱灌胃7 d诱导小鼠HVOD模型.动物处死后行血清肝功能指标榆测和全血细胞计数;肝组织切片HE染色、Masson三色染色,行组织学评分;RT-PCR检测肝组织内皮损伤相关因子内皮素-1（ET-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）以及纤溶酶原激活物抑制剂-1（PAI-1）的表达.结果：土三七组和野百合碱组成模率分别为80.0%和92.0%.两模型组小鼠体质量、肝指数、血清肝功能指标和全血细胞计数的变化以及肝组织学改变符合人类HVOD的临床和病理特征,肝组织ET-1、TNF-α、IL-1β和PAI-1 mRNA表达较正常对照组显著增高（P〈0.05）,其中土三七组PAI-1 mRNA表达显著高于野百合碱组（P〈0.05）.结论：土三七和野百合碱均可成功诱导小鼠HVOD模型,模型小鼠肝组织内皮损伤相关因子表达显著增高,提示内皮细胞损伤后内皮损伤相关因子的释放参与了HVOD的发生过程.

Expressions of Endothelial Injury-related Factors in Mice Model of Hepatic Veno-occlusive Disease

Background： Owing to the extensive use of herbal preparations, reports of hepatic veno-occlusive disease （HVOD） induced by taking herbs containing pyrrolizidine alkaloids （PAs） are increasing in China in recent years. Aims： To investigate the role of endothelial injury and its related factors in the pathogenesis of HVOD. Methods： Mice model of HVOD was induced by garage of Gynara segetum for 30 days and garage of monocrotaline for 7 days, respectively. Blood samples were harvested to perform liver function tests and complete blood count, Histological changes of liver tissue were evaluated by a scoring system in tissue slice stained by hematoxylin-eosin staining and by Masson triehrome staining. The expressions of endothelial injury-related factors, such as endothelin-1 （ET-1）, tumor necrosis factor-α（TNF-α） and i nterleukin-1β （IL-1β）, as well as plasminogen activator inhibitor-1 （PAI-1） in liver tissue were determined by RT-PCR. Results： The success rates of HVOD model construction by gavage of Gynura segetum and gavage of monocrotaline were 80.0% and 92.0%, respectively. Changes of body weight, liver index, liver function tests and complete blood count in mice with HVOD were consistent with those in human beings, so did the histological changes. Expressions of ET-1, TNF-ct, IL- l13 and PA]-I mRNA in liver tissue were significantly higher in mice with HVOD than those in the controls （P〈0.05）. Furthermore, expression of PAI-I mRNA was higher in Gyrtura segetum-indueed group than that in monocrotaline-induced group （P〈0.05）. Conclusions： Both Gynura segetum and monoerotaline can induce mice model of HVOD successfully. Expressions of endothelial injury-related factors increase significantly in liver tissue of mice with HVOD, which indicate that the release of related factors after endothelial injury is involved in the development of HVOD.