刀豆素蛋白A诱导小鼠肝纤维化模型的建立

Concanavalin A induced murine model for hepatic fibrosis

目的 建立小鼠的肝纤维化模型。方法 2 0只Balb c小鼠随机分 2组。实验组 (E组 )小鼠经尾静脉注射12 .5mg kg剂量的 1mol L刀豆素蛋白A(ConA) ,每周 1次 ,连续 6周 ;而对照组 (N组 )正常小鼠则相应地经尾静脉注射 2 5 0 μLPBS。每次注射ConA或PBS 2 4h后 ,经小鼠尾静脉取血检测ALT和AST。第 6次注射ConA一周后处死小鼠 ,取肝组织做HE染色及MassonTrichrome染色 ,显微镜下观察肝脏组织形态改变及胶原沉积情况。结果 与对照组比较 ,实验组小鼠的ALT和AST均明显升高 ,肝体积明显增大 ,表面不光滑 ,布满增生小结节。光镜下见肝组织结构紊乱 ,肝细胞坏死明显 ,有较多的淋巴细胞浸润。MassonTrichrome染色胶原明显增多。结论 反复静脉注射ConA可成功诱导建立小鼠肝纤维化模型。

Objective To establish a murine model for hepatic fibrosis with concanavalin A (Con A) induction. Methods Twenty Balb/c mice were randomly divided into 2 groups. In the experimental group (E), the mice were injected with 1 mol/L Con A at a dose of 12.5 mg/kg once a week for 6 weeks. In the control group (N), the mice were injected with 250 μL pyrogen-free PBS instead of Con A. Serum was extracted from individual mouse through the tail vein at 24 h after the injection. Hepatocellular injuries were evaluated by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. The mice were sacrificed at 1 week after the sixth/final injection of Con A. The morphological changes and collagen deposition of the liver tissue were observed by microscope after hematoxylin & eosin staining and Masson Trichrome staining. Results In contrast with group N, the levels of ALT and AST in group E were significantly increased, the volumes of liver enlarged remarkably, external surface of the liver was rough and studded with regenerated nodules. Destruction and necrosis of hepatocytes, and invasion of lymphocytes were found by microscopy. In addition, Masson Trichrome staining showed that the collagen deposition in liver parenchyma was obviously increased. Conclusion A murine model for hepatic fibrosis can be established by repeatedly administration of concanavalin A.