中文摘要：

目的探讨肝细胞向胆管上皮细胞转分化在继发性胆汁淤积性大鼠肝纤维化形成中的作用及黄芪汤组分抑制肝纤维化的效应机制。方法 75只SD雄性大鼠,采用胆总管结扎（bile duct ligation,BDL）制备继发性胆汁淤积性肝纤维化模型,假手术组（Sham）仅作胆总管分离,不作胆总管结扎。大鼠BDL术后1周随机分为对照组（M）与干预组（Y组,经灌胃给予黄芪汤组分4周）,Sham组于术后1周末随机抽取5只大鼠处死取材,M组分别于术后1、2、3、4周末随机抽取5只大鼠做动态观察,余下各组大鼠均于术后第5周末处死取材。观测肝脏组织学及羟脯氨酸（Hyp）含量;激光共聚焦显微镜观察肝组织胆管上皮细胞标志物角蛋白-7（CK7）与肝细胞特异性抗原（HepPar）共定位,Western blot检测CK7、HepPar的蛋白表达,IPP软件分析肝组织天狼猩红胶原染色。结果随着造模时间推移,M组大鼠肝组织肝细胞Hep Par阳性细胞逐渐减少（Sham〉M1周〉M2周〉M3周〉M4周〉M5周）,胆管上皮细胞（CK7阳性细胞）及纤维化程度、Hyp含量、CK7蛋白表达均逐渐增加（Sham〈M1周〈M2周〈M3周〈M4周〈M5周）,CK7/Hep Par共定位细胞于术后1周即见增加,术后3周达到峰值,然后渐趋减少,肝组织Hep par蛋白表达量与CK7蛋白表达量呈显著负相关,Hep Par阳性细胞表达量与CK7阳性细胞表达量、胶原沉积程度均呈显著负相关,而CK7阳性细胞表达量与胶原沉积程度呈显著正相关;与M组比较,Y组大鼠死亡率、CK7阳性细胞、纤维化程度、肝组织Hyp含量、CK7蛋白表达量均显著下降（P〈0.01）,Hep Par阳性细胞及Hep Par蛋白表达含量显著增加。结论肝细胞向胆管上皮细胞转分化可能是继发性胆汁淤积性大鼠肝纤维化形成过程中的关键病理环节,抑制肝细胞向胆管上皮细胞转分化可能是黄芪汤组分有效干预继发性胆汁淤积性肝纤维化的主要效应机制之一。

英文摘要：

Objective To investigate the mechanism of hepatocytes transdifferentiation to bile duct epithelial cells （BECs） and intervention of Huangqi decoction （HQD） on hepatic fibrosis formation in rats with secondary cholestasis. Methods Seventy-five SD male rats were made into cholestatic hepatic fibrosis model animals by bile duct ligation, and randomized into the control group （n=50） and the HQD group （n=15）. Starting from one week after modeling, they were administered orally with saline and HQD respectively for four weeks. Besides, a sham-operated group was set up with 10 rats operated by choledochus segregating only and administered after then with saline. Rats were killed in batches at different time points, i.e. each five from the control group and sham-operated group at the end of the 1st week, five from the control group for each time at the end of the 2nd, 3rd and 4th week, and all the remaining rats at the end of the 5th week. Their liver tissues were taken for histological change ...更多examination, content of hydroxyproline （Hyp） determination; protein expression of BECs marker cytokeratin 7 （CK7） and the hepatocyte specific antigen HepPar detection by Western blot, and CK7-HepPar co-localization by laser confocal microscopy. Then IPP software was used to analyze Sirius red stained positive areas of CK7 and Hep Par, as well as the average IOD of CK7/Hep Par co-localization. Results Hepatocytes in hepatic tissues （HepPar positive cell） in the model rats decreased gradually along was time went by after modeling （Sham〉M1w〉 M2w〉 M3w〉M4w〉 M5w）, which was in parallel with the increase of BECs （CK7 positive cells）, degree of fibrosis, Hyp content and CK7 protein expression. Increasing of co-localized positive cells of CK7/Hep Par began at 1 week and reached the peak 3 weeks after modeling, then it decreased gradually. The Hep Par protein expression was negatively correlated with that of CK7; the Hep Par positive cell expression was negatively correlated with CK7 posi