【Animal model】-Canine model of portal hypertension with carbon tetrachloride liver cirrhosis

  (1) Reproduction method Adult experimental dogs were given CCl4 by gavage at a dose of 2ml/kg body weight, twice in the first week and once a week thereafter for 12 weeks. After 12 weeks, they were anesthetized with 3% pentobarbital sodium The abdomen was opened, and the mean arterial pressure (MAP) was measured through the femoral artery catheterization to the abdominal aorta, and the portal pulse pressure (FPV) was measured through the mesenteric vessel catheterization to the main portal vein. The exposed portal vein and hepatic artery wall were respectively fitted with electromagnetic flowmeter probes, and connected to a multi-channel physiological recorder to record simultaneously. After the operation, the animals showed listlessness, lying still, weight loss, poor appetite, and occasionally vomiting after eating. The mortality rate of experimental animals was about 20%. After the operation, the pressure of the portal vein of the animals increased, the diameter of the portal vein increased, the blood flow of the whole liver and the intrahepatic resistance increased significantly. Pathological examination revealed that at 12 weeks, the dog’s liver was smaller than normal, and the liver was full of nodules of varying sizes. Under the microscope, hepatocytes lamellar degeneration and necrosis, nodular proliferation of hepatocytes, and obvious fibrous tissue proliferation, pseudo-lobule formation, and The microscopic findings of human liver cirrhosis after hepatitis are more consistent. Alanine aminotransferase and bilirubin are also elevated.

  (2) Features of the model This model is made by gavage CCl4, which avoids the effects of the oral method by the appetite of animals, and the shortcomings of the feeding method that are easy to enter the trachea. This method gives CCl4, the dose control is reliable, safe, the source of medicine is convenient, and the liver cirrhosis The formation rate is high and the time-consuming is not long. The pathological damage process of the liver cells is similar to the clinical one. The hemodynamic indicators such as portal pressure are significantly increased, and the indicators are stable, which is conducive to the study of drug efficacy.

  (3) Comparative medicine This model uses large animal dogs as model animals. Compared with liver cirrhosis models of small animals such as rats and rabbits, it is more meaningful for the study of the treatment of liver cirrhosis and portal hypertension, especially surgical treatment. The modeling drug CCl4 has strong selective hepatic cytotoxicity. It forms oxygen free radicals in the liver through the action of mixed peroxidase, initiates lipid peroxidation and damages liver cells. It can better simulate China's hepatitis as the main pathogenic factor The pathological process of liver cell necrosis, liver cirrhosis and portal hypertension, and the model lasts for a long time; this model is better than the prehepatic and posthepatic cirrhosis portal hypertension model, and it is a stable and reliable model that can better simulate human cirrhosis The animal model of portal hypertension is suitable for long-term research.