动物造模,肝硬化模型 z-bio 2021-12-27 297

　　(1) Breeding method Feed Liebert-Decal ethanol liquid feed to adult baboons. The feed formula consists of 18.6% casein, 0.23% L-cystine, 0.14% DL-methionine, 2.3% corn oil and 7.7 olive oil. Used 70.3% of sugars such as linoleic acid, ethyl linoleate, dextrin and maltose for 24 consecutive months (50% of the calories in sugar were replaced by ethanol). After modeling, the liver was taken out for histological morphological examination.

　　(2) Model characteristics: Fat infiltration, interstitial inflammation and fibrotic changes occurred in the liver of model animals, and one-third of the animals had obvious liver cirrhosis.

　　(3) Comparative medicine One of the causes of human liver cirrhosis is long-term excessive drinking. Ethanol is absorbed from the gastrointestinal tract and enters the liver. Under the action of alcohol dehydrogenase and microsomal oxidation system, ethanol is oxidized to acetic acid. In this process, coenzyme A (NAD) is converted into reduced coenzyme A (NADH). Reducing the ratio of NAD/NADH can inhibit the hepatic tricarboxylic acid circuit, weaken gluconeogenesis, reduce fatty acid oxidation, and increase synthesis. When triacylglycerols increase beyond the processing capacity of the liver, their accumulation in the liver will cause fatty infiltration of liver tissue, interstitial inflammation and fibrosis changes, and then cause liver cirrhosis. The establishment and successful replication of this model confirms that long-term excessive drinking can actually induce liver cirrhosis, and indicates that the existence of the above-mentioned mechanisms can lead to cirrhosis of the liver. Although this model conforms to the pathological characteristics of human alcoholic cirrhosis, the promotion and use of this method are strictly limited due to the high cost of experimental animals, long replication cycle and difficult management. Previously, it was believed that ethanol-induced liver cirrhosis was related to malnutrition, and it only occurred when it reached a certain level, because it was difficult to replicate the rat liver cirrhosis model by only feeding alcoholic food. In addition, ethanol itself will increase the body's demand for choline, and choline deficiency can cause liver cirrhosis. Therefore, the establishment of alcoholic liver cirrhosis models is usually reproduced by multi-factor synergistic methods (such as the combination of ethanol and CCl4). Ethanol can induce P450 activity and increase the liver toxicity of CCl4. Using CCl4 under the influence of ethanol-induced fatty liver can accelerate hepatocyte necrosis and significantly reduce modeling time. Both doses can be reduced at the same time to reduce side effects. Drugs and animals. Intolerance. According to reports, using this method to treat mice for 60 days can cause liver cirrhosis. The method is characterized by stable liver cirrhosis, clear staging, and low animal mortality. For example, use high-fat and low-protein food modeled on ethanol and carbon tetrachloride, take cornmeal as feed, add 20% lard and a small amount of cholesterol, and 30% alcohol as the only beverage, and use and inject 40 % CCl4 oil subcutaneously every 3 days. When the body weight is 5 ml/kg, liver cirrhosis can develop after six weeks. This method is easy to operate, has a higher molding rate (100%) and a lower mortality rate (20%). For example, mix phenobarbital sodium with alcohol and CCl4 to create a model. First, replace the solution containing phenobarbital sodium with drinking water to allow the animals to drink freely for two weeks. Then use a 50% to 60% CCl4 oil solution. Drinking water has only 10% to 30% ethanol solution, but the pathological examination after 9 weeks showed that the formation rate of pseudo lobules was 90% or higher.