Animal modeling drug efficacy evaluation - Tsukamoto French model

  (1) The replication method involves implanting a gastric tube into a rat during surgery and injecting ethanol and other nutrients daily using a liquid pump device. Ethanol accounts for 47% of total calories to maintain an ethanol concentration of 200-300mg/dl (2000-3000mg/L) in animal blood. After 10 weeks, whole blood was extracted to prepare serum for biochemical testing, and the liver was removed for histological examination.

  (2) The model features daily continuous injection of ethanol and other nutrients through a gastric tube for 10 weeks, leading to hepatic steatosis, hepatocyte degeneration, necrosis, and inflammation in the model animals. Liver fibrosis can form at 12-16 weeks. The main pathological features include hepatic steatosis, necrosis of the lobule center, inflammation around liver cells, and fibrosis around veins.

  (3) The pathological changes observed in animal liver in the Tsukamoto French model of comparative medicine are basically consistent with the pathological process of progressive alcoholic liver disease in humans, making it a good model for alcoholic liver disease. The biggest feature of this model is that the ethanol infusion dose can be set arbitrarily, which can maintain the ethanol content in animal blood at a certain level (generally 200-300mg/dl (2000-3000mg/L)). On this basis, while continuously injecting alcoholic liquid food, iron agents that enhance lipid peroxidation can be added. After 12-16 weeks, animal liver can undergo extensive fibrosis, including severe bridging fibrosis and cirrhosis. In addition, biochemical tests showed an increase in the content of malondialdehyde and hydroxyproline in the liver tissue of the model animal, indicating liver fibrosis caused by excessive lipid peroxidation. Due to the continuous and controllable ethanol injection in the Tsukamoto French model, some special equipment is required for model production. Although this model is widely used in international research on alcoholic liver disease, its high cost greatly limits its widespread application.