动物造模,肝衰竭 z-bo 2022-02-04 431

　　(1) Replication method Adult rats, thioacetamide (TAA) intraperitoneally injected 250-350mg/kg body weight, or subcutaneously injected 600mg/kg body weight, or gavage 300-400mg/kg body weight, 24 hours later, respectively The original dose and the same route were administered again. After administration, observe the general condition of the model animals continuously, record the time of death due to poisoning, at the same time, it is possible to record the electroencephalogram at different time points with the operation of embedding skull electrodes, and regularly draw blood for liver and kidney function measurement. When the model animals die or artificially After execution, his liver tissue was taken for pathological examination. During the entire experiment, the model animals used 10% glucose saline as the only drinking water, and a certain amount of 5% glucose injection could also be injected intravenously twice a day.

　　(2) Model characteristics: The model animals have yellow urine, lethargy, slow response to peripheral stimulation or progressively weakened 8 hours after the second administration. At 24 hours, the serum ALT, BT, and TNF-a increase abnormally, and then Although there is a trend of gradual decline, it has been maintained at a relatively high level within 72 hours. In addition, whole blood and plasma viscosity increased, hematocrit (HCT) increased, red blood cell aggregation index (EAI) increased, serum AST, BUN, λ-glutamyltransferase (GGT), lipoprotein-x (LP-x) , Endotoxin (ET) content increases, red blood cell stiffness index (IR) decreases. Pathological examination showed that the liver of the model animals was generally congested and enlarged, dark red, with rough particles on the surface; light microscopy showed large necrosis of the liver, edema and ballooning of liver cells, and inflammatory cell infiltration in the portal area, centered on the central vein , Liver lobules showed spot and focal necrosis. At this time, the model animals' righting reflex disappeared, and ataxias such as body tremors were obvious, and gradually developed into lethargy or coma over time. Some animals died, and the death time mostly occurred within 48 hours. There were bleeding and petechiae on the lips, tail, and feet of dead animals. In addition, the electroencephalogram of model animals showed the appearance of typical three-phase waves (delta waves) of hepatic encephalopathy.

　　(3) Comparative medicine Thioacetamide (TAA) is a kind of hepatotoxic substance. It is used to replicate animal models of liver failure. It has the typical characteristics of hepatic parenchymal cell damage and liver failure. The main manifestations are: serum ALT, AST, ALP activity increased, liver cell membrane Na+-K+-ATPase activity decreased, serum TBIL, BUN, ET content increased, plasma clotting factor level decreased, PT prolonged, whole blood and plasma viscosity increased, blood and intraventricular NH3, AAA and amino group The concentration of butyric acid and other neurotoxic substances increases, the frequency of EEG slows down, the amplitude increases, and the typical three-phase wave changes appear. The mechanism of TAA-induced liver failure can not only directly damage liver parenchymal cells, but also reduce the function of liver macrophages and the formation of intestinal endotoxemia, which further aggravates the damage to liver tissue. Experiments have shown that different doses of TAA are significantly related to the severity of liver parenchymal cell damage and hepatic encephalopathy in model animals. The higher the dose of TAA, the higher the level of endotoxin and blood ammonia, the more obvious liver function damage and liver pathological changes, and the higher the grade score of hepatic encephalopathy. There is an obvious dose-effect relationship. For example, intraperitoneal injection of TAA 250mg/kg body weight or 350mg/kg body weight, although both doses can cause 100% of animals to develop clinical hepatic encephalopathy, the former is mostly graded 1 to 2 without animal death, while the latter is graded Most of them are grade 3 to 4, and the animal mortality rate is 41.7%. Because this model method is simple and inexpensive, and compared with the animal model of acute liver failure caused by D-GLA liver failure, the model has clear characteristics, relatively slow course of disease, and easy-to-master stage. Therefore, it has received more attention from domestic and foreign researchers in recent years. Pay attention and apply. However, this model is generally limited to small animals as model objects, so its wide range of use is limited.