尿激酶型纤溶原激活物基因缺失型(uPA^(-/-))小鼠肝纤维化模型的病理学研究

Pathologic study of liver fibrosis animal model using uPA knock-out mice

目的采用uPA基因缺失(uPA-/-)小鼠构建肝纤维化动物模型,并进行病理学比较研究。方法选取成年雄性BL/6J野生型和uPA-/-基因缺失型小鼠,分为4组:对照组(WT,uPA-/-)和模型组(WT,uPA-/-),每组10只。模型组小鼠腹腔注射10%CCl40.15 ml,对照组小鼠腹腔注射橄榄油0.15 ml,每周2次,连续6周。称取动物体重和肝脏等脏器重量,计算脏器系数;取肝脏做大体病理观察;用HE染色和Masson三色胶原染色观察组织病理学改变;并进行电镜超微结构观察。结果与野生模型组小鼠相比,uPA-/-模型组小鼠的肝脏纤维化程度更加严重。表现为肝脏重量和肝脏系数的显著增加(P>0.05);大体观察肝脏肿大、色灰暗发白、出现颗粒状结节;HE染色、Masson染色和电镜超微结构检查均提示uPA-/-模型组小鼠肝细胞破坏严重,胶原纤维沉积更广泛,并形成了假小叶。结论 uPA-/-模型组的肝脏纤维化程度比WT模型组明显严重,uPA-/-小鼠是建立肝纤维化模型的易感品系。

Objective To build liver fibrosis models using uPA knock-out（uPA-/-） mice and observe the pathologic changes.Methods Adult male BL/6J WT mice and uPA knock-out（uPA-/-） mice were divided into four groups with 10 mice in each group： control groups（WT,uPA-/-） and liver fibrosis model groups（WT,uPA-/-）.Mice were intraperitoneally injected 0.15 ml 10% CCl4（or olive oil as control） twice per week for 6 weeks.Animal body weight,liver weight,spleen weight and kidney weight were measured,and organ coefficients were calculated.General pathology of livers was observed at sacrifice,histopathology was performed using HE staining and Masson staining,and electron microscopic exam was performed to observe the ultrastructural changes.Results Liver weight and liver coefficient of uPA-/-model mice increased significantly compared with WT model mice（P0.05）.The enlargement of the liver,pale gray color,and apparent granular nodules were observed in uPA-/-model mice.HE staining,Masson staining and electron microscopy all showed in consistency that liver cells were severely damaged,extensive collagen was deposited and false lobules were formed in uPA-/-model mice.Conclusion uPA-/-model mice shows more severe liver fibrosis compared with WT mice.uPA-/-mice are susceptible animal strain to establish liver fibrosis model.