中文摘要：

目的：探讨建立胆汁淤积小鼠模型的可行性。方法胆管结扎（bile duct ligation，BDL）模型：手术结扎C57BL／6小鼠胆总管后关腹并设立假手术对照组，10 d 后处死小鼠，留取肝脏观察其病理变化。3，5-二乙氧基羰基-1，4-二氢-2，4，6-三甲基吡啶（3，5-diethoxycarbonyl-1，4-dihydrocollidine，DDC）模型：喂养含0．1％DDC 饲料的 C57BL／6小鼠。两周后处死，留取肝脏观察其病理变化。2-辛炔酸-牛血清白蛋白（2-octynoic acid-bovine serum albumin，2OA-BSA）模型：分别于0、3周时对 C57BL／6小鼠腹腔内注射100μg 的2OA-BSA，第8周时处死小鼠，留取肝脏观察其病理变化。显性阴性转移生长因子β受体 II （dominant-negative form of the human transforming growth factor-beta receptor II，dnTGF-βR II）转基因小鼠：取16周龄 dnTGF-βR II 转基因小鼠，留取肝脏观察其病理变化。结果四种造模小鼠病理切片均可见肝细胞损伤以及汇管区大量炎症细胞浸润，汇管区炎症分级统计如下：BDL 模型小鼠2．7±0．5；DDC 模型小鼠2．9±0．6；2OA-BSA 模型小鼠1．5±0．5；dnTGF-βR II 转基因小鼠1．2±0．6，与各自对照组相比均有显著统计学差异（P ＜0．01）。其中，BDL 和 DDC 模型以大胆管损伤为主；而2OA-BSA 模型和 dnTGF-βR II 转基因小鼠模型以小胆管损伤为主。结论上述4种小鼠胆汁淤积造模方法的可行，且形成周期短，稳定可靠。

英文摘要：

Objective To establish and evaluate the cholestatic mice models induced by bile duct ligation （BDL）in C57BL/6 mice,3,5-diethoxycarbonyl-1 ,4-dihydrocollidine （DDC）-fed C57BL/6 mice,2-octynoic acid （2OA）coupled to bovine serum albumin （BSA）-immunized C57BL/6 mice,and dominant-negative form of the human transforming growth factor,beta receptor II （dnTGF-βR II）transgenic mice.Methods BDL mice：the bile ducts of mice were occluded by 1igation.A sham operation group was set as control.After 10 days,liver tissue was collected from mice.DDC-fed mice：mice were fed by a 0.1 % DDC-supplemented diet for 2 weeks and liver tissues were collected.2OA-BSA immunized mice：mice were immunized with a mixture of 2OA-BSA conjugate intraperitoneally at week 0 and 3.Liver tissues were collected from mice at week 8 after the initial immunization.DnTGF-βR II transgenic mice：liver tissues were collected from 16-week-old mice. Pathological changes of liver tissues in aforementioned four groups were evaluated by hematoxylin and eosin （HE）staining.Results Amount of inflammatory cells infiltration and liver cells damage were observed in four mice models.Hepatic inflammatory degrees of BDL mice,DDC-fed mice,2OA-BSA immunized mice and dnTGF-βR II were 2.7 ±0.5,2.9 ±0.6,1 .5 ±0.5,and 1 .2 ±0.6,respectively.The level of inflammatory cells infiltrating in portal area in mice models was higher than that in control group,respectively.Furthermore,larger bile ducts damages were found in BDL mice and DDC-fed mice.On the other hand,intrahepatic small bile ducts damages were observed in 2OA-BSA immunized mice and dnTGF-βR II transgenic mice.Conclusion The models of cholestasis induced by BDL mice,DDC-fed mice,2OA-BSA immunized mice,and dnTGF-βR II transgenic mice are ideal study models of cholestasis because of their stable methods and short process cycle.