动物造模,肝衰竭模型 z-bio 2021-03-24 592

　　(1) Breeding method Adult male rats are forcibly taken orally with 10 ml/kg body weight of 40% CCl4 oil solution, or adult dogs are intraperitoneally injected with 0.9 ml/kg body weight of 50% CCl4 oil solution. The color is the skin of the animal. Observe appetite and activity . Under normal circumstances after administration, the time of death is recorded, and blood is collected regularly or dynamically to prepare serum for liver function examination, and liver tissue is extracted for pathological examination. Large animals can continue to be used for B-ultrasound and EEG examination of the liver.

　　(2) Model characteristics: The activity of model rats began to decrease significantly after 12 hours of intragastric administration of CCl4; at 24 hours, they were very dull, did not eat or drink and were caught, and they had no resistance during exercise. Their hair is rough and irregular, and their urine is yellow. At the same time, ALT and TBIL increased significantly, liver volume increased significantly (decreased one by one), yellow color, fragile texture and large areas of necrosis. Hepatocytes were observed under a microscope, a small amount of neutrophils infiltrated into the necrotic area, most of the lobular structure disappeared, no fibrosis, nodules of hepatocyte regeneration; at this time, some animals had hemorrhage under the orbital skin, and the animals had died. Within 48 hours, the mortality of model animals reached 85.7%. Two to three days after the drug was injected into the experimental dogs, all the animals showed varying degrees of vomiting, only drinking water without eating, and their response to external stimuli was slowed and paralyzed. Then I was in a coma. Some animals have high fever and gastrointestinal tract. Bleeding, jaundice, and even progressive death. Three days after the injection of the drug, the serum ALT, TBIL, NH3, and PT of the model animals gradually increased or prolonged, while the GLU gradually decreased. EEG examination showed common slow wave, Q wave, triangle wave and three-phase wave. B-ultrasound examination showed that the size of the liver was reduced to varying degrees. Within 48 to 96 hours, the mortality rate of model animals reached more than 73.0%. Regular autopsy and pathological examination showed that the liver of the model animals shrank in size, the liver capsule shrank, and the color was uneven. Under the microscope, most liver cells are lysed and necrotic, and the sine wave is enlarged and filled. It is not clear that there are a small number of hepatocytes in the peripheral blood vessels of the liver lobules, including red blood cells, showing degeneration and hyperemia, most of which are lymphocytes, with a large number of inflammatory cell infiltration and liver proliferation. Kill the liver cells of dead animals and make them necrotic. The heart, lungs and kidneys are swollen to different degrees, bleeding, necrosis and inflammatory cells are slightly infiltrated.

　　(3) Comparative medicine CCl4 is one of the most classic drug-induced liver injury model toxins. It is mainly metabolized by the liver's microsomal cytochrome P450 oxidase to produce non-trichloromethyl and non-trichloromethyl peroxygen substances, destroy the integrity of the cell membrane structure and function, and allow it to pass through the liver cell membrane . The exudation of a large amount of soluble enzymes eventually leads to the death of liver cells, leading to liver failure. The mechanism of CCl4 metabolism and liver toxicity allows the replication of various liver injury models. Among them, dosage and administration method are important technologies. Usually high-dose oral or intraperitoneal injections are used to reproduce the acute liver failure model. For gastric administration, CCl4 is absorbed from the portal system and directly enters the liver. Intraperitoneal injection has a large absorption area, and toxins are quickly and completely absorbed. After absorption, it mainly enters the portal circulation and first reaches the liver. When selecting animals, rodents often use stomach administration, while large animals prefer intraperitoneal or intravenous injections. CCl4 is more commonly used because of its relatively clear toxicity mechanism, low cost, convenient experimental operation and high reproducibility, which can reproduce liver failure models. However, the toxic effect of CCl4 on liver cells is due to the generation of oxygen free radicals that can damage cell membranes and lipid peroxidation. The liver cells around the central vein are very fragile and do not match the tissue characteristics. Necrosis of human liver cells. In addition, injecting large amounts of CCl4 may damage other organs, especially the lungs and kidneys, because they are not completely metabolized in the liver. In addition, it is difficult to observe clinical signs of deep hepatic coma in model animals.