Ge Xinlan, Xu Dabin, Pan Ke, Mao Guankun, Lu Shichun, Li Chonghui
Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Exp Ther Med. 2022 Nov 2;24(6):739. doi: 10.3892/etm.2022.11675. eCollection 2022 Dec.
Due to the lack of a suitable model, research on biliary biology is far behind that on other organs. A mouse model of common bile duct (CBD) dilation (BDD) was first established and compared with CBD ligation mice (BDL). Then, in a transplantation experiment, the dilated CBD of recipient BDD mice was injured by making an elliptical incision and repaired by transplanting a bile duct patch from donor BDD mice. Biochemical and histological changes were analyzed and cell proliferation of the bile duct grafts was determined. Slightly dilated and unblocked CBD with a diameter of 2.89±0.76 mm was obtained in BDD mice, while the CBD diameter was 0.51±0.08 mm in the Sham group and 4.71±0.64 mm in the BDL group on day 14 after surgery. The liver damage was very mild in BDD mice compared with BDL mice, proving that the BDD model could be further used for bile duct transplantation. By cross transplanting the bile duct patch from enhanced green fluorescence protein and wild-type BDD mice, it was found that the CBD injury was well repaired and the cells of the bile duct patch were completely replaced by recipient-derived cells at 12 week after the repair operation. α Smooth muscle actin, Ki67 and cytokeratin 19 immunofluorescence staining showed that the proliferation of bile duct epithelial cells and abundant active fibroblasts were found within the bile duct patch during the regeneration process. Therefore, a reliable new mouse model of bile duct injury and repair was successfully established and can be used in the study of biliary repair mechanisms and tissue engineering of biliary ducts.
由于缺乏合适的模型,胆管生物学的研究远远落后于其他器官的研究。首先建立了胆总管(CBD)扩张(BDD)的小鼠模型,并与胆总管结扎小鼠(BDL)进行比较。然后,在一项移植实验中,通过椭圆形切口损伤受体BDD小鼠扩张的CBD,并通过移植供体BDD小鼠的胆管补片进行修复。分析生化和组织学变化,并确定胆管移植物的细胞增殖情况。BDD小鼠获得了直径为2.89±0.76 mm的轻度扩张且未阻塞的CBD,而假手术组在术后第14天的CBD直径为0.51±0.08 mm,BDL组为4.71±0.64 mm。与BDL小鼠相比,BDD小鼠的肝损伤非常轻微,证明BDD模型可进一步用于胆管移植。通过交叉移植增强型绿色荧光蛋白和野生型BDD小鼠的胆管补片,发现修复手术后12周时,CBD损伤得到良好修复,胆管补片的细胞完全被受体来源的细胞取代。α平滑肌肌动蛋白、Ki67和细胞角蛋白19免疫荧光染色显示,再生过程中胆管补片内发现胆管上皮细胞增殖且有丰富的活性成纤维细胞。因此,成功建立了一种可靠的胆管损伤和修复新小鼠模型,可用于胆管修复机制和胆管组织工程的研究。