动物造模,药效评价,急性肝损伤 z-bio 2024-08-20 340

　　1. Modeling material animals: rats weighing 200-250g, or mice weighing 20-25g, regardless of gender; Drug: Carbon tetrachloride (CCl4).

　　2. Modeling method: Rats were injected intraperitoneally or subcutaneously with 1ml/kg of carbon tetrachloride solution at once; Mice were orally or intraperitoneally injected with 0.1-1% CCl4 olive oil solution at a dose of 10-20ml/kg.

　　3. Modeling principle: After carbon tetrachloride enters the body, it is metabolized by cytochrome P-450 dependent mixed function oxidase in the endoplasmic reticulum of liver cells, generating active trichloromethyl radicals and chloride radicals. These free radicals can covalently bind to large molecules inside and on the cell membrane, causing loss of enzyme function, lipid peroxidation of the cell membrane, increased cytoplasmic Ca2+concentration, leading to liver cell damage, and transaminase infiltration into the bloodstream.

　　4. The morphological changes after modeling include necrosis and steatosis in the central region of the liver lobules; The serological indicators are elevated ALT and aspartate aminotransferase (AST). Generally, after 3 hours of administration of carbon tetrachloride, ALT and AST begin to increase and reach their peak after 12-13 hours, with the highest reaching 10 times the normal value. Afterwards, they show a downward trend and can return to normal after 90 hours.