动物造模,脂肪肝 z-bo 2022-02-02 379

　　[Modeling method]: Methionine-choline deficiency (MCD) diet is usually used to induce classic NAFLD animal models. The MCD diet is rich in carbohydrates (40%) and fat (10%), but lacks methionine and choline, which are involved in the oxidation of fatty acid β in liver cells and the synthesis of low-density lipoproteins.

　　High-fat diet (HFD) model: Use HFD (carbohydrates, fat and protein accounted for 52%, 30% and 18% of total calories respectively) fed to rats, guinea pigs, rabbits, dogs, etc. May trigger. ..

　　Total Parenteral Nutrition (TPN) model: adult rat deep vein (such as superior vena cava) cannulation. Connect the infusion pump to continuously inject the non-protein nutrient solution (such as high glucose + amino acid high nutrient solution or glucose + fat emulsion). Tsukamato-French rat model: In 1984, Tsukamato-French et al. surgically implanted a gastric tube into the rat, and continued to inject a liquid diet containing ethanol to increase the blood ethanol concentration of the rat to 200-300 mg /dl. Three models were kept for several months, or at the same time, the gastric tube was fed with a liquid diet for 30 days. The liquid diet contained a small amount of fixed-calorie corn oil (4.9% calories).

　　Ethanol gavage model: Gavage of coarse feed and ethanol (11-12 g/kg) daily for 4 weeks in rats can cause liver tissue damage, similar to the Tsukamato-French method. Once a day (5ml/100g), provide high-quality sake (about 60 degrees) for the stomach, lack of nutrient feed (wheat flour, sub-flour, glass powder, soybean powder, according to the ratio of 2:1:1:1) A small amount of soybean oil is added to it and salt is added), and then after oral gavage on an empty stomach, fasting every night until the next morning, and then feeding can ingest alcoholic fatty liver for 75 consecutive days. The mixture of wine, corn oil and pyrazole (liquid 8-12g/kg, corn 2g/kg, pyrazole 24mg/kg) can also be used for tube feeding, and the modeling time is 12 weeks.

　　[Model Features]: Simple and easy to implement, but the disease and its degree are related to the sex, strain and type of the mouse. Obvious hepatic steatosis appeared in mice of 1-2 weeks of age, and liver appeared after 2 weeks. Necrotizing inflammation in turn causes fibrosis of the periosteum and central peripheral vein, and is accompanied by the up-regulation of serum transaminase and lipid oxidase gene expression in the liver. Oxidative stress slightly increases transaminase at the 5th week, and liver inflammation and necrosis at the 12th week. Fibrosis. MCD-fed mice lose muscle and body fat content after losing weight, and 4 weeks after modeling, insulin-sensitive peripheral tissues will develop hypoglycemia.

　　HFD model: Sporadic fatty liver occurred 4 weeks after modeling, simple fatty liver 8 weeks, steatohepatitis 12 weeks, hepatitis increased and necrosis, steatitis, steatosis 16 weeks, inflammation was slightly reduced within 24 weeks, but fibrosis It became severe and even intermittent fibrosis appeared. Rat abdominal visceral fat increased, peripheral blood free fatty acids and total cholesterol gradually increased, accompanied by portal vein endotoxemia, liver cell mitochondrial damage, oxidative stress, lipid peroxidation damage and liver Kupffer cell activity. There is insulin resistance, but weight gain and blood TG increase are unclear.

　　TPN model: If the non-protein energy of the nutrient solution exceeds 33% or the total intake exceeds 83% of the total calories, the liver of the rat will heal in one week, and obvious steatosis will appear. Using a high-nutrient solution containing high glucose and amino acids requires 146% of non-protein energy [equivalent to 350 (kg?d) non-protein calories] and 335% of nitrogen [equivalent to 2.7g amino acid nitrogen kg? D)], hepatomegaly appeared in 1/2 day, and liver glycogen and fat increased after 2 days. By day 4, liver fat had increased fourfold, and the lack of essential fatty acids in the liver gradually increased. Ethanol tube feeding model: The animal's body weight increases slowly, and the food intake is significantly reduced. Most animal feces are loose. Histopathology showed hepatocellular edema and balloon-like changes, a large number of round lipid droplets of varying sizes in the cytoplasm, and the formation of regular or irregular bodies of eosinophils (ethanolic vitreous). It is a significant infiltration of inflammatory cells in the portal vein area, collagen fibers also proliferate, and sinus sinus endothelial cells swell.