The Experimental Study Of The Rat Extrahepatic Bile Duct Ligation Time On The Selection Of Surgical Timing

Objective: Based on the bile duct closed injury models of ligating the bile ducts of SD rats, this paper researches the choledochojejunostomy performed at different time points after bile duct obstruction, explores the dynamic pathological changes of liver, bile duct and the expression of TGF-β1, collagen in bile duct, and provides clinical reference for surgical timing selection.Methods: 1. Establish animal models of bile duct closed injury, measure the liver function, pathological changes of liver, bile duct and bile duct dilatation trending at different time points. 2. According to the degree of liver fibrosis and different bile duct expansion extent, choledochojejunostomy was performed at 7d, 14d, 21d after ligation, selects stained with hematoxylin&eosin (H&E) were analyzed for histological and morphology of liver and bile duct. The expression levels of TGF-β1 and collagen were determined by immunohistochemical technique.Results:1. After the establishment of bile duct closed injury models, the liver function of SD rats showed different changes from that of human beings. The expansion of bile duct reached the peak at the time of 14 days after ligation and accompanied with liver fibrosis, gallbladder wall thickening, mucous membrane shedding and extensive proliferation of collagen fibers.2. The expression levels of TGF-β1 and collagen in bile ducts increased significantly alonge with the ligation time prolonging(P<0.05). 30 days after portoenterostomy, liver cell structure returned to the normal and lobular fibrous tissue disappeared in the 7-day ligation group and 14-day ligation group, while in the 21-day group, we still could see the liver fibrosis and the formation of false lobules, and the damage of liver was irreversible. The changes of TGF-β1, collagen expression in bile duct was coincident and they returned to normal levels in 30 days after portoenterostomy. There was no significant difference between the 7-day and 14-day ligation groups(P>0.05). However, the expression levels of TGF-β1, collagen of bile duct in the 21-day ligation group was significantly higher than that of 7-day and 14-day groups(P<0.05). It suggested that the expression levels of TGF-β1 was increased alonge with the time of ligation, the increased amount of TGF-β1 may lead to oversynthesis of collagen, focal accumulation of collagen in bile duct and restenosis of anastomosis eventually.Conclusion:1. The method of ligating rat common bile duct is simple, with high success rate, favourable reproducibility and stability way to establish bile duct closed injury model which is mimic to pathophysical features of human damaged bile duct.2. The optimal surgical timing for treating closed bile duct injury caused by ligating rat extrahepatic bile duct is 1 to 2 weeks after the injury, with that the common bile duct has expanded to a suitable degree, and liver fibrosis has not occurred. the implementation of biliary-enteric reconstruction as soon as possible, and the resulting narrow may be reduced for scar tissue after bile duct hyperplasia.