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

  (1) Breeding method Take 2 ml/kg body weight of CCl4 orally twice a week for adult dogs for the first 12 weeks, orally once a week for 12 weeks, and then use 3% pentobarbital sodium anesthesia after 12 weeks. Open the abdomen, and measure the mean arterial pressure (MAP) through the femoral artery cannulation to the abdominal aorta, and measure the portal vein pressure (FPV) through the mesenteric vessel cannulation to the main portal vein. Electromagnetic flowmeter probes are respectively connected to the bare portal vein and hepatic artery wall, and connected to a multi-channel physiological recorder for simultaneous recording. After the operation, these animals showed discomfort, lying down, weight loss, loss of appetite and vomiting after meals. The mortality rate of experimental animals was about 20%. After the operation, the pressure of the animal's portal vein increases, the diameter of the portal vein increases, and the blood flow and intrahepatic resistance of the whole liver increase significantly. Pathological examination showed that at the 12th week, the dog's liver was smaller than normal, and the liver was full of nodules of various sizes. Under the microscope, the hierarchical degeneration and necrosis of hepatocytes, nodular hyperplasia of hepatocytes, obvious fibrous tissue hyperplasia, the formation of pseudolobules and the microscopic findings of human liver cirrhosis after hepatocyte inflammation are more consistent. Alanine aminotransferase and bilirubin are also elevated.

  (2) Features of the model This model is composed of CCl4 in the stomach, which avoids the influence of oral animals' appetite, and avoids the shortcomings of feeding, because it easily enters the trachea. This method provides CCl4 and reliable dose control. Safe and convenient source of medicines. The formation rate of liver cirrhosis is high and takes time. The pathological damage process of liver cells is similar to the clinical one. Hemodynamic indicators (such as portal pressure) increase significantly, and these indicators are stable and useful for studying drug efficacy.

  (3) Comparative Medicine This model uses a large animal dog as a model animal. Compared with liver cirrhosis models of small animals (such as rats and rabbits), it is more meaningful in the treatment of liver cirrhosis and portal hypertension. Especially surgical treatment. The modeling drug CCl4 has strong selective hepatotoxicity. The action of mixed peroxidase forms oxygen free radicals in the liver, triggers lipid peroxidation, and damages liver cells. In my country, I can better simulate hepatitis as the main virulence factor. Hepatocyte necrosis, liver cirrhosis, portal hypertension, the model lasts for a long time. This model is superior to the portal hypertension model before and after cirrhosis, and it is a stable and reliable model that can better simulate human cirrhosis. The portal hypertension model is suitable for long-term research.