肝衰竭模型,动物造模 z-bio 2021-03-24 852

　　(1) Reproduction method Adult rats, intraperitoneal injection of thioacetamide (TAA) 250-350 mg/kg body weight, subcutaneous injection of 600 mg/kg body weight, or oral gavage method of 300-400 mg/kg body weight, each Rats after 24 hours. Perform the same route again. After the administration, the overall condition of the model animals was continuously observed and the time of death from poisoning was recorded. On the other hand, skull electrodes can be implanted to record EEG at various time points, and blood can be drawn regularly to measure liver and kidney function. .. If the model animal dies or is executed manually, the liver tissue will be harvested for pathological examination. Throughout the experiment, the model animals used 10% dextrose saline as the only drinking water, or injected a fixed amount of 5% dextrose injection twice a day.

　　(2) Model characteristics: 8 hours after the second administration, the model animal has a yellowish, drowsy, slow or gradually weakened response to surrounding stimuli. Serum ALT, BT and TNF-a increased abnormally within 24 hours. After that, it gradually decreased and remained at a high level within 72 hours. In addition, whole blood and plasma viscosity increased, hematocrit (HCT) increased, erythrocyte aggregation index (EAI) increased, serum AST, BUN, λ-glutamyltransferase (GGT), lipoprotein-x (LP).- x), increase endotoxin (ET) content and reduce red blood cell stiffness index (IR). Pathological examination showed that the liver of model animals was usually congested and swollen, and the surface was dark red with coarse particles. Optical microscopy showed extensive necrosis of the liver, edema and liver cell balance, and inflammatory cell infiltration in the hilar area. The liver lobules were spotted and locally necrotic, centered on the central vein. At this time, the recovery reflex of the model animals disappeared, the ataxia such as body tremor became obvious, and gradually became lethargic and coma over time, some animals died, and the death time was close to 48 hours. Within an hour. The dead animals have bleeding and ecchymosis on their lips, tail and paws. In addition, the electroencephalogram of the model animal showed the typical three-phase wave (delta wave) of hepatic encephalopathy.

　　(3) Comparative Medicine Thioacetamide (TAA) is a hepatotoxic substance used to replicate animal liver failure models. It has the typical characteristics of liver parenchymal cell damage and liver failure. The main symptoms are: increased serum ALT, AST and ALP activities, decreased hepatocyte membrane Na + -K + -ATPase activity, increased serum TBIL, BUN, ET levels, decreased plasma clotting factor levels, prolonged PT, overall viscosity, blood and Intraventricular NH3 concentration increases, neurotoxic substances (such as AAA GABA and GABA), EEG frequency decreases and wave amplitude increases, and wave changes occur. In addition to direct damage to liver parenchymal cells, TAA-induced liver failure can also reduce the function of liver macrophages and the formation of endotoxemia, thereby damaging liver tissue and making it worse. Experiments have shown that in model animals, different doses of TAA are significantly related to the severity of liver parenchymal cell damage and hepatic encephalopathy. The higher the TAA dose, the higher the endotoxin and blood ammonia levels, the more obvious liver damage and liver pathological changes, and the higher the score of hepatic encephalopathy. There is an obvious dose-effect relationship. For example, intraperitoneal injection of TAA 250 mg/kg body weight or 350 mg/kg body weight can cause clinical hepatic encephalopathy in 100% of animals at two doses, but most of the former are classified as 1-2 and death. Most of them are grade 3-4, and the animal mortality rate is 41.7%. In recent years, compared with the animal model of acute liver failure caused by D-GLA liver failure, this model is simple, cheap, with clear features, relatively slow course of disease, and easy to learn. Researchers at home and abroad. Please pay attention and apply. However, this model is usually limited to small animals as model objects, so it has a wide range of uses.