动物造模,肝硬化动物模型 z-bio 2021-11-15 472

　　(1) Replication method Adult male rats are injected intraperitoneally with 0.5% dimethylnitrosamine (DMNA) 3 days a week, at a dose of 10 mg/kg body weight, once a day for 4 weeks. Or, inject thioacetamide (TAA) intraperitoneally at a dose of 100 mg/kg of body weight, double the initial dose, and then once every 2 days for 1 week / 2 days, or use distilled water for TAA to make only 0.03% Solution solution. Feed water for 12 weeks for animals to drink. Alternatively, select adult mice and inject 10% D-galactosamine (DGA) intraperitoneally at a dose of 250 mg/kg body weight, once a day, 6 times a week, for 6 months. After modeling, collect whole blood and liver for biochemical and histomorphological examination.

　　(2) The model is a 2-4 week DMNA model, including serum alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) activity, serum total bilirubin TBIL and total bile acid. Function (TBA). The content of hydroxyproline (Hyp) in the liver tissue increases while the content of albumin (Alb) decreases. The liver tissue shows extensive hemorrhage and necrosis, inflammatory cell infiltration, liver sinusoid wall cells, and diffuse pseudo-leaf formation in fibrous tissue. This is sexual hyperplasia, forming thick, complete intervals. Twelve weeks after TAA modeling, serum growth hormone (GH) levels in liver tissues increased, insulin-like growth factor I (IGF-I) levels decreased, and IGF-I mRNA expression levels also decreased. formed. Six months after DGA modeling, the model animals showed progressive biliary hyperplasia and fibrous septum formation.

　　(3) Comparative medicine. Chemical substances including drugs are one of the important causes of liver damage and cirrhosis. Clinically, the mechanism of drug-induced liver disease varies from species to species and is very complex, but it can be divided into two main types. Direct cytotoxicity and specific reactions. The liver damage caused by the former is usually predictable, specific to a specific drug, and related to the dose of the drug, while the latter rarely occurs in some sensitive individuals, and it is difficult to predict whether it will occur and has nothing to do with the dose. For example, isoniazid causes a mild and transient increase in transaminase in 20% of patients, and will gradually develop into chronic hepatitis and cirrhosis after 1 year of continuous use. Therefore, low-dose and long-term continuous use are usually necessary prerequisites for drugs and chemicals that cause human liver cirrhosis, and are also an important step in replicating animal models of liver cirrhosis. Long-term use of low-dose carcinogens can cause liver cirrhosis and liver cancer. Common carcinogens used for modeling include DMNA, diethylnitrosamine (DENA) and TAA. The liver is the main organ of its metabolism, so once it enters the body, the damaged part of the body is mainly liver cells. For example, DMNA can be converted into effective alkylates through microsomal transformation, thereby destroying intracellular macromolecules. In the acute phase, asinazone 3 can cause necrosis and lipid changes, while in the chronic phase, liver fibrosis, cirrhosis and liver tumors can form. Among them, TAA metabolism is an electrophilic active group product, which can interfere with the migration of RNA in the liver cell nucleus, affect protein synthesis and enzyme activity, increase nuclear DNA synthesis and mitosis, and promote development. For liver cirrhosis; a small dose of TAA can induce liver cell apoptosis, a large dose can cause lipid oxidation and lobular necrosis, and the changes in liver fibrous tissue are close to the manifestations of human liver cirrhosis; long-term use of DGA can also cause liver fibrosis, liver cirrhosis and liver cancer Can be induced. DGA is not a pure liquid that directly kills liver cells, but an inducer that acts indirectly. After DGA enters the human body, it will cause the liver to capture uridine triphosphate (UTP), glycogen, RNA, glycoprotein synthesis, glutathione depletion, hepatic macrophage activation and massive release of TNF-α. It causes functional and structural damage to liver cells, and induces liver tissue necrosis and liver cell apoptosis. DMNA, DENA, TA model features: easy to operate and stable model, can study the pathological process of liver cirrhosis portal hypertension and the mechanism from cirrhosis to liver cancer, but it is highly toxic and volatile, expensive and can be imitate. The rate is not high. The characteristics of the DGA model: The dose-dependent pathological changes are similar to viral hepatitis. The pathological process of liver cirrhosis and portal hypertension is observed, and the reversibility of liver fibrosis is also studied. Although the model can be reproduced well, the dose of the model is expensive, and the animals are prone to liver cirrhosis and have a high mortality rate, which limits the widespread use and wide application of the model.