目的：制作亚急性肝内胆汁淤积动物模型，探索其发生的生化和病理变化过程。方法幼年SD大鼠40只，分为α-萘异硫氰酸酯（ ANIT）模型组和对照组，分别给予ANIT及芝麻油灌胃，1次／周，共4次，每次灌胃后48 h处死一批大鼠，取血标本送检肝功能生化指标，留取肝脏标本观察肝脏以及胆管病理改变。结果 ANIT灌胃后48 h，血转氨酶、胆红素明显上升，肝脏出现结构坏死，炎症细胞浸润、增生，胆管增生，第9天、第16天上述病变逐渐加重，第23天肝脏生化指标逐渐恢复，肝脏结构好转，胆管增生和纤维化仍明显。结论成功制作幼鼠亚急性胆汁淤积的动物模型，ANIT每周一次灌胃后2～3周内胆汁淤积的生化和病理改变明显，第4周逐渐恢复，但胆管增生和肝纤维化仍然明显。%Objective To manufacture the sub-acute intrahepatic cholestasis model with infantile rats and explore the biochemical and pathological changes .Methods Male SD infantile rats (150~180 g, n=40 ) were randomly di-vided into two groups .The ANIT ( alpha-naphthyl-isothiocyanate ) model group was lavaged with four weekly doses of ANIT (80 mg/kg), the control group was lavaged with same volume of placebo sesame oil .Eight rats were sacrificed af-ter 48 hour ANIT treatment every week .The blood samples were collected to assess AST , ALT, TBIL, DBIL, TBA, ALP and GGT, and the liver samples were made into paraffin sections and observed with microscope .Results Serum ALT, TBIL, DBIL, TBA, ALP and GGT were increased after 48 hour ANIT treatment, and maintained at the high level until the third week.In the fourth week, the serum ALT, TBIL, DBIL, ALP were declined quickly, however the serum TBA and GGT remained rising .Pathological changes were obvious after 48 h first ANIT treatment , characterizing with liver necrosis , inflammatory infiltration , bile duct hyperplasia , which appeared gradually increasing until the third week . In the fourth week , the liver necrosis and inflammatory infiltration recovered normal , but the bile duct hyperplasia and liver fibrosis remained aggravating .Conclusion The sub-acute intraheptic cholestasis model is manufactured successful-ly with the ANIT lavaging weekly .The cholestasis changes are the most obvious in the second and third week , but reco-vere in the fourth week except the bile duct hyperplasia and liver fibrosis .
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