Date Published: June 03, 2019
Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Author(s): Wei-wei Luo, Xue-ling Zhou, Qing-qing Wang, Yan-jing Shao, Ze-ming Li, Dong-kang Zhao, Shui-ping Yu.
To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis.
90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology.
Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group.
Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.
Obstructive jaundice is a kind of clinically common disease, mainly caused by cholestasis1. The bile outflow pathway is narrow or the bile can not enter the digestive tract after obstruction. It can cause pathophysiological disorders of the body, and eventually lead to intestinal flora imbalance and dysfunction, combined with severe septic shock and systemic multiple organ failure2. Obstructive jaundice often has an acute onset, rapid development, and high mortality3. The animal model of obstructive jaundice is an important part of the study of hepatobiliary diseases, and it is the basis for studying the pathogenesis of various hepatobiliary diseases, evaluating the therapeutic effect and drug development. Most of the existing obstructive jaundice animal models are constructed by bile duct ligation and biliary surgery4,5, which is not only complicated to operate, but has a lower survival rate of more than 3 weeks6. Moreover, the pathogenesis of obstructive jaundice caused by this method is quite different from that of clinical cholelithiasis. Clinically, the cause of obstruction, such as cholelithiasis, is characterized by gallstones or common bile duct stones. Under the action of dilated biliary tract and bile duct endothelial cells, stones enter and block the common bile duct and intrahepatic bile duct. The site of the disease is in the lumen, and the degree of obstruction is not completely blocked7,8. Animal models constructed by traditional bile duct ligation or biliary surgery cannot simulate this series of pathological processes, and the results may be affected. This study found that the injection of Compont gel in the common bile duct of rats can construct an animal model that is closer to the pathogenesis of clinical obstructive jaundice, and the survival rate is higher than 3 weeks.
The classic bile duct ligation method covers almost all biliary models, including obstructive jaundice models, bile internal and external drainage models, and so on4,5. It has a wide range of applications, but the model principle of this classic procedure is to rely on external force to block the biliary tract, which is different from the pathogenesis of clinical biliary diseases. There are many kinds of diseases that can cause obstructive jaundice in clinical practice. Only a few are complete obstruction of biliary tract caused by tumor compression. Most of them are cholelithiasis and chronic biliary obstruction. Their pathogenesis is that obstruction directly blocks biliary tract or biliary tract stenosis. Ulcers and scars formed by detachment of bile duct epithelial cells can aggravate biliary stricture. The rupture and relaxation of muscle fibers of the wall can lead to biliary dilatation, suggesting that biliary endothelial cells are closely related to biliary stricture. Therefore, we speculate that clinical biliary occlusion or compression stenosis, its pathogenesis may involve the role of biliary endothelial cells and wall muscles. Obviously, the ligation model of the classical method does not fully apply these changes. In addition, biliary obstruction caused by clinical diseases is often chronic development, and the course of disease is repeated. The biliary tract alternates with obstruction and recanalization under the intervention of the body itself or medical measures. Except for congenital biliary atresia, there are few diseases with complete obstruction. Thus, the classic common bile duct ligation does not seem to be applicable to all studies of biliary diseases, especially chronic obstructive biliary diseases. Therefore, exploring animal models that are closer to the pathogenesis of clinical chronic obstructive jaundice has potential application value.
The obstructive jaundice model produced by our group, Compont gel can contact bile duct without damaging the bile duct endothelium, and then can form incomplete obstruction, and the obstruction time is longer, which is more effective to simulate the pathogenesis of clinically common diseases that cause obstructive jaundice. The chronic obstructive jaundice model formed by injection of Compont gel can be used for the study of chronic biliary tract disease, stent stenosis and biliary tract injury, and provides a more ideal animal model for clinical disease research.